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  • 1. Abdissa, Negera
    et al.
    Induli, Martha
    Fitzpatrick, Paul
    Alao, John Patrick
    Sunnerhagen, Per
    Landberg, Göran
    Yenesew, Abiy
    Erdelyi, Mate
    Cytotoxic quinones from the roots of Aloe dawei.2014Inngår i: Molecules, ISSN 1420-3049, E-ISSN 1420-3049, Vol. 19, nr 3, s. 3264-3273Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Seven naphthoquinones and nine anthraquinones were isolated from the roots of Aloe dawei by chromatographic separation. The purified metabolites were identified by NMR and MS analyses. Out of the sixteen quinones, 6-hydroxy-3,5-dimethoxy-2-methyl-1,4-naphthoquinone is a new compound. Two of the isolates, 5,8-dihydroxy-3-methoxy-2-methylnaphthalene-1,4-dione and 1-hydroxy-8-methoxy-3-methylanthraquinone showed high cytotoxic activity (IC₅₀ 1.15 and 4.85 µM) on MCF-7 breast cancer cells, whereas the others showed moderate to low cytotoxic activity against MDA-MB-231 (ER Negative) and MCF-7 (ER Positive) cancer cells.

  • 2.
    Ali, Sara E.
    et al.
    German Univ Cairo, Fac Pharm & Biotechnol, Dept Pharmaceut Biol, New Cairo 12613, Egypt.
    El Gedaily, Rania A.
    Cairo Univ, Fac Pharm, Pharmacognosy Dept, Kasr el Aini St, Cairo 11562, Egypt.
    Mocan, Andrei
    Iuliu Hatieganu Univ Med & Pharm, Dept Pharmaceut Bot, Cluj Napoca 400337, Romania.
    Farag, Mohamed A.
    Cairo Univ, Fac Pharm, Pharmacognosy Dept, Kasr el Aini St, Cairo 11562, Egypt;Amer Univ Cairo, Sch Sci & Engn, Dept Chem, New Cairo 11835, Egypt.
    El-Seedi, Hesham R.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Farmakognosi. Menoufia Univ, Fac Sci, Shibin Al Kawm 32512, Egypt.
    Profiling Metabolites and Biological Activities of Sugarcane (Saccharum officinarum Linn.) Juice and Its Product Molasses via a Multiplex Metabolomics Approach2019Inngår i: Molecules, ISSN 1420-3049, E-ISSN 1420-3049, Vol. 24, nr 5, artikkel-id 934Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Sugarcane (Saccharum officinarum L.) is an important perennial grass in the Poaceae family cultivated worldwide due to its economical and medicinal value. In this study, a combined approach using mass spectrometry (MS) and nuclear magnetic resonance (NMR) spectroscopy was employed for the large-scale metabolite profiling of sugarcane juice and its by-product molasses. The polyphenols were analysed via UPLC-UV-ESI-MS, whereas the primary metabolites such as sugars and organic and amino acids were profiled using NMR spectroscopy and gas chromatography/mass spectrometry (GC/MS). UPLC/MS was more effective than NMR spectroscopy or GC/MS for determining differences among the metabolite compositions of the products. Under the optimized conditions, UPLC/MS led to the identification of 42 metabolites, including nine flavonoids, nine fatty acids, and two sterols. C/O Flavone glycosides were the main subclass detected, with tricin-7-O-deoxyhexosyl glucuronide being detected in sugarcane and molasses for the first time. Based on GC/MS analysis, disaccharides were the predominant species in the sugarcane juice and molasses, with sucrose accounting for 66% and 59%, respectively, by mass of all identified metabolites. The phenolic profiles of sugarcane and molasses were further investigated in relation to their in vitro antioxidant activities using free radical scavenging assays such as 2,2-Diphenyl-1-picrylhydrazyl free radical-scavenging ability (DPPH), Trolox equivalent antioxidant capacity (TEAC) and ferric reducing antioxidant power (FRAP). In view of its higher total phenolic content (TPC) (196 +/- 2.1 mg GAE/100 g extract) compared to that of sugarcane juice (93 +/- 2.9 mg GAE/100 g extract), molasses exhibited a substantially higher antioxidant effect. Interestingly, both extracts were also found to inhibit alpha-glucosidase and alpha-amylase enzymes, suggesting a possible antihyperglycaemic effect. These findings suggest molasses may be a new source of natural antioxidants for functional foods.

  • 3. Atilaw, Yoseph
    et al.
    Duffy, Sandra
    Heydenreich, Matthias
    Muiva-Mutisya, Lois
    Avery, Vicky M
    Erdelyi, Mate
    Yenesew, Abiy
    Three Chalconoids and a Pterocarpene from the Roots of Tephrosia aequilata.2017Inngår i: Molecules, ISSN 1420-3049, E-ISSN 1420-3049, Vol. 22, nr 2, artikkel-id E318Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    In our search for new antiplasmodial agents, the CH₂Cl₂/CH₃OH (1:1) extract of the roots of Tephrosia aequilata was investigated, and observed to cause 100% mortality of the chloroquine-sensitive (3D7) strain of Plasmodium falciparum at a 10 mg/mL concentration. From this extract three new chalconoids, E-2',6'-dimethoxy-3',4'-(2'',2''-dimethyl)pyranoretrochalcone (1, aequichalcone A), Z-2',6'-dimethoxy-3',4'-(2'',2''-dimethyl)pyranoretrochalcone (2, aequichalcone B), 4''-ethoxy-3''-hydroxypraecansone B (3, aequichalcone C) and a new pterocarpene, 3,4:8,9-dimethylenedioxy-6a,11a-pterocarpene (4), along with seven known compounds were isolated. The purified compounds were characterized by NMR spectroscopic and mass spectrometric analyses. Compound 1 slowly converts into 2 in solution, and thus the latter may have been enriched, or formed, during the extraction and separation process. The isomeric compounds 1 and 2 were both observed in the crude extract. Some of the isolated constituents showed good to moderate antiplasmodial activity against the chloroquine-sensitive (3D7) strain of Plasmodium falciparum.

  • 4. Atilaw, Yoseph
    et al.
    Muiva-Mutisya, Lois
    Ndakala, Albert
    Akala, Hoseah M
    Yeda, Redemptah
    Wu, Yu J
    Coghi, Paolo
    Wong, Vincent K W
    Erdelyi, Mate
    Yenesew, Abiy
    Four Prenylflavone Derivatives with Antiplasmodial Activities from the Stem of Tephrosia purpurea subsp. leptostachya.2017Inngår i: Molecules, ISSN 1420-3049, E-ISSN 1420-3049, Vol. 22, nr 9, artikkel-id E1514Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Four new flavones with modified prenyl groups, namely (E)-5-hydroxytephrostachin (1), purleptone (2), (E)-5-hydroxyanhydrotephrostachin (3), and terpurlepflavone (4), along with seven known compounds (5-11), were isolated from the CH₂Cl₂/MeOH (1:1) extract of the stem of Tephrosia purpurea subsp. leptostachya, a widely used medicinal plant. Their structures were elucidated on the basis of NMR spectroscopic and mass spectrometric evidence. Some of the isolated compounds showed antiplasmodial activity against the chloroquine-sensitive D6 strains of Plasmodium falciparum, with (E)-5-hydroxytephrostachin (1) being the most active, IC50 1.7 ± 0.1 μM, with relatively low cytotoxicity, IC50 > 21 μM, against four cell-lines.

  • 5.
    Benchoula, Khaled
    et al.
    Int Islamic Univ Malaysia, Kulliyyah Pharm, Dept Basic Med Sci, Kuantan 25200, Pahang, Malaysia.
    Khatib, Alfi
    Int Islamic Univ Malaysia, Kulliyyah Pharm, Dept Pharmaceut Chem, Kuantan 25200, Pahang, Malaysia.
    Quzwain, Fairuz M. C.
    Univ Jambi, Fac Med, Jambi 36122, Indonesia.
    Mohamad, Che Anuar Che
    Int Islamic Univ Malaysia, Kulliyyah Pharm, Dept Basic Med Sci, Kuantan 25200, Pahang, Malaysia.
    Sulaiman, Wan Mohd Azizi Wan
    Int Islamic Univ Malaysia, Kulliyyah Pharm, Dept Basic Med Sci, Kuantan 25200, Pahang, Malaysia.
    Wahab, Ridhwan Abdul
    Int Islamic Univ Malaysia, Dept Biomed Sci, Kulliyyah Allied Hlth Sci, Kuantan 25200, Pahang, Malaysia.
    Ahmed, Qamar Uddin
    Int Islamic Univ Malaysia, Kulliyyah Pharm, Dept Pharmaceut Chem, Kuantan 25200, Pahang, Malaysia.
    Ghaffar, Majid Abdul
    Int Islamic Univ Malaysia, Kulliyyah Pharm, Dept Pharmaceut Chem, Kuantan 25200, Pahang, Malaysia.
    Saiman, Mohd Zuwairi
    Univ Malaya, Inst Biol Sci, Fac Sci, Kuala Lumpur 50603, Malaysia.
    Alajmi, Mohamed F.
    King Saud Univ, Dept Pharmacognosy, Coll Pharm, Riyadh 11451, Saudi Arabia.
    El-Seedi, Hesham
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Farmakognosi.
    Optimization of Hyperglycemic Induction in Zebrafish and Evaluation of Its Blood Glucose Level and Metabolite Fingerprint Treated with Psychotria malayana Jack Leaf Extract2019Inngår i: Molecules, ISSN 1420-3049, E-ISSN 1420-3049, Vol. 24, nr 8, artikkel-id 1506Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    A standard protocol to develop type 1 diabetes in zebrafish is still uncertain due to unpredictable factors. In this study, an optimized protocol was developed and used to evaluate the anti-diabetic activity of Psychotria malayana leaf. The aims of this study were to develop a type 1 diabetic adult zebrafish model and to evaluate the anti-diabetic activity of the plant extract on the developed model. The ability of streptozotocin and alloxan at a different dose to elevate the blood glucose levels in zebrafish was evaluated. While the anti-diabetic activity of P. malayana aqueous extract was evaluated through analysis of blood glucose and LC-MS analysis fingerprinting. The results indicated that a single intraperitoneal injection of 300 mg/kg alloxan was the optimal dose to elevate the fasting blood glucose in zebrafish. Furthermore, the plant extract at 1, 2, and 3 g/kg significantly reduced blood glucose levels in the diabetic zebrafish. In addition, LC-MS-based fingerprinting indicated that 3 g/kg plant extract more effective than other doses. Phytosterols, sugar alcohols, sugar acid, free fatty acids, cyclitols, phenolics, and alkaloid were detected in the extract using GC-MS. In conclusion, P. malayana leaf aqueous extract showed anti-diabetic activity on the developed type 1 diabetic zebrafish model.

  • 6.
    Bergman, Sara
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Avdelningen för organisk farmaceutisk kemi.
    Brandt, Peter
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Avdelningen för organisk farmaceutisk kemi.
    Nordeman, Patrik
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Avdelningen för organisk farmaceutisk kemi.
    Larhed, Mats
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Avdelningen för organisk farmaceutisk kemi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Odell, Luke R.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Avdelningen för organisk farmaceutisk kemi.
    Eriksson, Jonas
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Avdelningen för organisk farmaceutisk kemi.
    Synthesis of 11C-Labelled Ureas by Palladium(II)-Mediated Oxidative Carbonylation2017Inngår i: Molecules, ISSN 1420-3049, E-ISSN 1420-3049, Vol. 22, nr 10, artikkel-id 1688Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Positron emission tomography is an imaging technique with applications in clinical settings as well as in basic research for the study of biological processes. A PET tracer, a biologically active molecule where a positron-emitting radioisotope such as carbon-11 has been incorporated, is used for the studies. Development of robust methods for incorporation of the radioisotope is therefore of the utmost importance. The urea functional group is present in many biologically active compounds and is thus an attractive target for incorporation of carbon-11 in the form of [C-11] carbon monoxide. Starting with amines and [C-11] carbon monoxide, both symmetrical and unsymmetrical C-11-labelled ureas were synthesised via a palladium(II)-mediated oxidative carbonylation and obtained in decay-corrected radiochemical yields up to 65%. The added advantage of using [C-11] carbon monoxide was shown by the molar activity obtained for an inhibitor of soluble epoxide hydrolase (247 GBq/mu mol-319 GBq/mu mol). DFT calculations were found to support a reaction mechanism proceeding through an C-11-labelled isocyanate intermediate.

  • 7.
    Blom, Magnus
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Syntetisk organisk kemi.
    Norrehed, Sara
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Syntetisk organisk kemi.
    Andersson, Claes-Henrik
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Syntetisk organisk kemi.
    Huang, Hao
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Tekniska sektionen, Institutionen för teknikvetenskaper, Nanoteknologi och funktionella material.
    Light, Mark E.
    Department of Chemistry, University of Southampton, Highfield, Southampton SO17 1BJ, U.K.
    Bergquist, Jonas
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Analytisk kemi.
    Grennberg, Helena
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Fysikalisk-organisk kemi.
    Gogoll, Adolf
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Syntetisk organisk kemi.
    Synthesis and Properties of Bis-Porphyrin Molecular Tweezers: Effects of Spacer Flexibility on Binding and Supramolecular Chirogenesis2016Inngår i: Molecules, ISSN 1420-3049, E-ISSN 1420-3049, Vol. 21, nr 1Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Abstract: Ditopic binding of various dinitrogen compounds to three bisporphyrin molecular tweezers with spacers of varying conformational rigidity, incorporating the planar ene-diyne (1), the helical stiff stilbene (2), or the semirigid glycoluril motif fused to  the porphyrins (3) are compared. Binding constants Ka = 10^4 to 10^6 M^-1 reveal subtle  differences between these tweezers, that are discussed in terms of porphyrin dislocation  modes. Exciton coupled circular dichroism (ECCD) of complexes with chiral dinitrogen  guests provides experimental evidence for the conformational properties of the tweezers. The results are further supported and rationalized by conformational analysis.

  • 8.
    Borroto-Escuela, Dasiel O.
    et al.
    Karolinska Inst, Dept Neurosci, Retzius Vag 8, S-17177 Stockholm, Sweden;Univ Urbino Carlo Bo, Dept Biomol Sci, I-61029 Urbino, Italy;Observ Cubano Neurociencias, Grp Bohio Estudio, Zaya 50, Yaguajay 62100, Cuba.
    Narvaez, Manuel
    Univ Malaga, Inst Invest Biomed Malaga, Fac Med, E-29071 Malaga, Spain.
    Ambrogini, Patrizia
    Univ Urbino Carlo Bo, Dept Biomol Sci, I-61029 Urbino, Italy.
    Ferraro, Luca
    Univ Ferrara, SVEB, Dept Life Sci & Biotechnol, I-44121 Ferrara, Italy.
    Brito, Ismel
    Karolinska Inst, Dept Neurosci, Retzius Vag 8, S-17177 Stockholm, Sweden;Observ Cubano Neurociencias, Grp Bohio Estudio, Zaya 50, Yaguajay 62100, Cuba.
    Romero Fernandez, Wilber
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för cell- och molekylärbiologi, Beräkningsbiologi och bioinformatik.
    Andrade-Talavera, Yuniesky
    Karolinska Inst, Dept Neurobiol Care Sci & Soc, Ctr Alzheimer Res, Neuronal Oscillat Lab, S-17177 Stockholm, Sweden.
    Flores-Burgess, Antonio
    Univ Malaga, Inst Invest Biomed Malaga, Fac Med, E-29071 Malaga, Spain.
    Millon, Carmelo
    Univ Malaga, Inst Invest Biomed Malaga, Fac Med, E-29071 Malaga, Spain.
    Gago, Belen
    Univ Malaga, Inst Invest Biomed Malaga, Fac Med, E-29071 Malaga, Spain.
    Angel Narvaez, Jose
    Univ Malaga, Inst Invest Biomed Malaga, Fac Med, E-29071 Malaga, Spain.
    Odagaki, Yuji
    Saitama Med Univ, Dept Psychiat, Saitama 3388570, Japan.
    Palkovits, Miklos
    Semmelweis Univ, Fac Med, Dept Anat Histol & Embryol, H-1094 Budapest, Hungary.
    Diaz-Cabiale, Zaida
    Univ Malaga, Inst Invest Biomed Malaga, Fac Med, E-29071 Malaga, Spain.
    Fuxe, Kjell
    Karolinska Inst, Dept Neurosci, Retzius Vag 8, S-17177 Stockholm, Sweden.
    Receptor-Receptor Interactions in Multiple 5-HT1A Heteroreceptor Complexes in Raphe-Hippocampal 5-HT Transmission and Their Relevance for Depression and Its Treatment2018Inngår i: Molecules, ISSN 1420-3049, E-ISSN 1420-3049, Vol. 23, nr 6, artikkel-id 1341Artikkel, forskningsoversikt (Fagfellevurdert)
    Abstract [en]

    Due to the binding to a number of proteins to the receptor protomers in receptor heteromers in the brain, the term "heteroreceptor complexes" was introduced. A number of serotonin 5-HT1A heteroreceptor complexes were recently found to be linked to the ascending 5-HT pathways known to have a significant role in depression. The 5-HT1A-FGFR1 heteroreceptor complexes were involved in synergistically enhancing neuroplasticity in the hippocampus and in the dorsal raphe 5-HT nerve cells. The 5-HT1A protomer significantly increased FGFR1 protomer signaling in wild-type rats. Disturbances in the 5-HT1A-FGFR1 heteroreceptor complexes in the raphe-hippocampal 5-HT system were found in a genetic rat model of depression (Flinders sensitive line (FSL) rats). Deficits in FSL rats were observed in the ability of combined FGFR1 and 5-HT1A agonist cotreatment to produce antidepressant-like effects. It may in part reflect a failure of FGFR1 treatment to uncouple the 5-HT1A postjunctional receptors and autoreceptors from the hippocampal and dorsal raphe GIRK channels, respectively. This may result in maintained inhibition of hippocampal pyramidal nerve cell and dorsal raphe 5-HT nerve cell firing. Also, 5-HT1A-5-HT2A isoreceptor complexes were recently demonstrated to exist in the hippocampus and limbic cortex. They may play a role in depression through an ability of 5-HT2A protomer signaling to inhibit the 5-HT1A protomer recognition and signaling. Finally, galanin (1-15) was reported to enhance the antidepressant effects of fluoxetine through the putative formation of GalR1-GalR2-5-HT1A heteroreceptor complexes. Taken together, these novel 5-HT1A receptor complexes offer new targets for treatment of depression.

  • 9.
    Denisova V, Aleksandra
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - Ångström, Molekylär biomimetik.
    Tibbelin, Julius
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC.
    Emanuelsson, Rikard
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Tekniska sektionen, Institutionen för teknikvetenskaper, Nanoteknologi och funktionella material.
    Ottosson, Henrik
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - Ångström, Molekylär biomimetik.
    A Computational Investigation of the Substituent Effects on Geometric, Electronic, and Optical Properties of Siloles and 1,4-Disilacyclohexa-2,5-dienes2017Inngår i: Molecules, ISSN 1420-3049, E-ISSN 1420-3049, Vol. 22, nr 3, artikkel-id 370Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Thirty two differently substituted siloles 1a–1p and 1,4-disilacyclohexa-2,5-dienes 2a–2p were investigated by quantum chemical calculations using the PBE0 hybrid density functional theory (DFT) method. The substituents included σ-electron donating and withdrawing, as well as π-electron donating and withdrawing groups, and their effects when placed at the Si atom(s) or at the C atoms were examined. Focus was placed on geometries, frontier orbital energies and the energies of the first allowed electronic excitations. We analyzed the variation in energies between the orbitals which correspond to HOMO and LUMO for the two parent species, here represented as ΔεHL, motivated by the fact that the first allowed transitions involve excitation between these orbitals. Even though ΔεHL and the excitation energies are lower for siloles than for 1,4-disilacyclohexa-2,5-dienes the latter display significantly larger variations with substitution. The ΔεHL of the siloles vary within 4.57–5.35 eV (ΔΔεHL = 0.78 eV) while for the 1,4-disilacyclohexa-2,5-dienes the range is 5.49–7.15 eV (ΔΔεHL = 1.66 eV). The excitation energy of the first allowed transitions display a moderate variation for siloles (3.60–4.41 eV) whereas the variation for 1,4-disilacyclohexa-2,5-dienes is nearly doubled (4.69–6.21 eV). Cyclobutadisiloles combine the characteristics of siloles and 1,4-disilacyclohexa-2,5-diene by having even lower excitation energies than siloles yet also extensive variation in excitation energies to substitution of 1,4-disilacyclohexa-2,5-dienes (3.47–4.77 eV, variation of 1.30 eV).

  • 10.
    Díaz-Álvarez, Alba E.
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC.
    Mesas-Sánchez, Laura
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC.
    Dinér, Peter
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC. KTH-Royal Institute of Technology.
    Access to optically pure β-hydroxy esters via non-enzymatic kinetic resolution by a planar-chiral DMAP catalyst2014Inngår i: Molecules, ISSN 1420-3049, E-ISSN 1420-3049, Vol. 19, nr 9, s. 14273-14291Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The development of new approaches to obtain optically pure β-hydroxy esters is an important area in synthetic organic chemistry since they are precursors of other high value compounds. Herein, the kinetic resolution of racemic β-hydroxy esters using a planar-chiral DMAP derivative catalyst is presented. Following this procedure, a range of aromatic β-hydroxy esters was obtained in excellent selectivities (up to = 107) and high enantiomeric excess (up to 99% ee). Furthermore, the utility of the present method was demonstrated in the synthesis of (S)-3-hydroxy-N-methyl-3-phenylpropanamide, a key intermediate for bioactive molecules such as fluoxetine, tomoxetine or nisoxetine, in its enantiomerically pure form.

  • 11.
    Edueng, Khadijah
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för farmaci. International Islamic University Malaysia.
    Mahlin, Denny
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för farmaci. Astra Zeneca.
    Gråsjö, Johan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för farmaci.
    Nylander, Olivia
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för farmaci.
    Thakrani, Manish
    Department of Pharmacy, University College London, UK.
    Bergström, Christel
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för farmaci.
    Supersaturation Potential of Amorphous Active Pharmaceutical Ingredients after Long-Term Storage2019Inngår i: Molecules, ISSN 1420-3049, E-ISSN 1420-3049, Vol. 24, nr 15, artikkel-id 2731Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    This study explores the effect of physical aging and/or crystallization on the supersaturation potential and crystallization kinetics of amorphous active pharmaceutical ingredients (APIs). Spray-dried, fully amorphous indapamide, metolazone, glibenclamide, hydrocortisone, hydrochlorothiazide, ketoconazole, and sulfathiazole were used as model APIs. The parameters used to assess the supersaturation potential and crystallization kinetics were the maximum supersaturation concentration (Cmax,app), the area under the curve (AUC), and the crystallization rate constant (k). These were compared for freshly spray-dried and aged/crystallized samples. Aged samples were stored at 75% relative humidity for 168 days (6 months) or until they were completely crystallized, whichever came first. The solid-state changes were monitored with differential scanning calorimetry, Raman spectroscopy, and powder X-ray diffraction. Supersaturation potential and crystallization kinetics were investigated using a tenfold supersaturation ratio compared to the thermodynamic solubility using the µDISS Profiler. The physically aged indapamide and metolazone and the minimally crystallized glibenclamide and hydrocortisone did not show significant differences in their Cmax,app and AUC when compared to the freshly spray-dried samples. Ketoconazole, with a crystalline content of 23%, reduced its Cmax,app and AUC by 50%, with Cmax,app being the same as the crystalline solubility. The AUC of aged metolazone, one of the two compounds that remained completely amorphous after storage, significantly improved as the crystallization kinetics significantly decreased. Glibenclamide improved the most in its supersaturation potential from amorphization. The study also revealed that, besides solid-state crystallization during storage, crystallization during dissolution and its corresponding pathway may significantly compromise the supersaturation potential of fully amorphous APIs.

  • 12.
    El-Aarag, Bishoy
    et al.
    Menoufia Univ, Fac Sci, Chem Dept, Biochem Div, Shibin Al Kawm 32512, Egypt;Okayama Univ, Grad Sch Nat Sci & Technol, Div Chem & Biotechnol, Okayama 7008530, Japan.
    Magdy, Mohamed
    Menoufia Univ, Dept Chem, Fac Sci, Shibin Al Kawm 32512, Egypt.
    AlAjmi, Mohamed F.
    King Saud Univ, Dept Pharmacognosy, Coll Pharm, Riyadh 11451, Saudi Arabia.
    Khalifa, Shaden A. M.
    Stockholm Univ, Wenner Gren Inst, Dept Mol Biosci, S-10691 Stockholm, Sweden.
    El-Seedi, Hesham
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Farmakognosi. Menoufia Univ, Dept Chem, Fac Sci, Shibin Al Kawm 32512, Egypt;Univ Karachi, Int Ctr Chem & Biol Sci, Karachi 75270, Pakistan.
    Melittin Exerts Beneficial Effects on Paraquat-Induced Lung Injuries in Mice by Modifying Oxidative Stress and Apoptosis2019Inngår i: Molecules, ISSN 1420-3049, E-ISSN 1420-3049, Vol. 24, nr 8, artikkel-id 1498Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Melittin (MEL) is a 26-amino acid peptide with numerous biological activities. Paraquat (PQ) is one of the most widely used herbicides, although it is extremely toxic to humans. To date, PQ poisoning has no effective treatment, and therefore the current study aimed to assess for the first time the possible effects of MEL on PQ-induced lung injuries in mice. Mice received a single intraperitoneal (IP) injection of PQ (30 mg/kg), followed by IP treatment with MEL (0.1 and 0.5 mg/kg) twice per week for four consecutive weeks. Histological alterations, oxidative stress, and apoptosis in the lungs were studied. Hematoxylin and eosin (H&E) staining indicated that MEL markedly reduced lung injuries induced by PQ. Furthermore, treatment with MEL increased superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) activity, and decreased malonaldehyde (MDA) and nitric oxide (NO) levels in lung tissue homogenates. Moreover, immunohistochemical staining showed that B-cell lymphoma-2 (Bcl-2) and survivin expressions were upregulated after MEL treatment, while Ki-67 expression was downregulated. The high dose of MEL was more effective than the low dose in all experiments. In summary, MEL efficiently reduced PQ-induced lung injuries in mice. Specific pharmacological examinations are required to determine the effectiveness of MEL in cases of human PQ poisoning.

  • 13.
    El-Saied, Fathy
    et al.
    Menoufia Univ, Fac Sci, Dept Chem, Shibin Al Kawm 32512, Egypt.
    El-Aarag, Bishoy
    Menoufia Univ, Fac Sci, Chem Dept, Biochem Div, Shibin Al Kawm 32512, Egypt;Okayama Univ, Div Chem & Biotechnol, Grad Sch Nat Sci & Technol, Okayama 7008530, Japan.
    Salem, Tarek
    Univ Sadat City, Genet Engn & Biotechnol Inst, Dept Mol Biol, Sadat City 32958, Egypt.
    Said, Ghada
    Menoufia Univ, Fac Sci, Dept Chem, Shibin Al Kawm 32512, Egypt.
    Khalifa, Shaden A. M.
    Stockholm Univ, Wenner Gren Inst, Dept Mol Biosci, SE-10691 Stockholm, Sweden;Novum, Dept Expt Canc Med ECM, S-14157 Stockholm, Sweden.
    El-Seedi, Hesham
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Farmakognosi. Menoufia Univ, Fac Sci, Dept Chem, Shibin Al Kawm 32512, Egypt;Jiangsu Univ, Int Res Ctr Food Nutr & Safety, Zhenjiang 212013, Jiangsu, Peoples R China;Al Rayan Coll, Al Rayan Res & Innovat Ctr, Medina 42541, Saudi Arabia.
    Synthesis, Characterization, and In Vivo Anti-Cancer Activity of New Metal Complexes Derived from Isatin-N(4)antipyrinethiosemicarbazone Ligand Against Ehrlich Ascites Carcinoma Cells2019Inngår i: Molecules, ISSN 1420-3049, E-ISSN 1420-3049, Vol. 24, nr 18, artikkel-id 3313Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The current study aimed to synthesize new metal coordination complexes with potential biomedical applications. Metal complexes were prepared via the reaction of isatin-N(4)anti- pyrinethiosemicarbazone ligand 1 with Cu(II), Ni(II), Co(II), Zn(II), and Fe(III) ions. The obtained metal complexes 2-12 were characterized using elemental, spectral (H-1-NMR, EPR, Mass, IR, UV-Vis) and thermal (TGA) techniques, as well as magnetic moment and molar conductance measurements. In addition, their geometries were studied using EPR and UV-Vis spectroscopy. To evaluate the in vivo anti-cancer activities of these complexes, the ligand 1 and its metal complexes 2, 7 and 9 were tested against solid tumors. The solid tumors were induced by subcutaneous (SC) injection of Ehrlich ascites carcinoma (EAC) cells in mice. The impact of the selected complexes on the reduction of tumor volume was determined. Also, the expression levels of vascular endothelial growth factor (VEGF) and cysteine aspartyl-specific protease-7 (caspase-7) in tumor and liver tissues of mice bearing EAC tumor were determined. Moreover, their effects on alanine transaminase (ALT), aspartate transaminase (AST), albumin, and glucose levels were measured. The results revealed that the tested compounds, especially complex 9, reduced tumor volume, inhibited the expression of VEGF, and induced the expression of caspase-7. Additionally, they restored the levels of ALT, AST, albumin, and glucose close to their normal levels. Taken together, our newly synthesized metal complexes are promising anti-cancer agents against solid tumors induced by EAC cells as supported by the inhibition of VEGF and induction of caspase-7.

  • 14. Endale, Milkyas
    et al.
    Ekberg, Annabel
    Alao, John Patrick
    Akala, Hoseah M
    Ndakala, Albert
    Sunnerhagen, Per
    Erdelyi, Mate
    Yenesew, Abiy
    Anthraquinones of the roots of Pentas micrantha.2013Inngår i: Molecules, ISSN 1420-3049, E-ISSN 1420-3049, Vol. 18, s. 311-321Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Pentas micrantha is used in the East African indigenous medicine to treat malaria. In the first investigation of this plant, the crude methanol root extract showed moderate antiplasmodial activity against the W2- (3.37 μg/mL) and D6-strains (4.00 μg/mL) of Plasmodium falciparum and low cytotoxicity (>450 μg/mL, MCF-7 cell line). Chromatographic separation of the extract yielded nine anthraquinones, of which 5,6-dihydroxylucidin-11-O-methyl ether is new. Isolation of a munjistin derivative from the genus Pentas is reported here for the first time. The isolated constituents were identified by NMR and mass spectrometric techniques and showed low antiplasmodial activities.

  • 15.
    Farag, Mohamed A.
    et al.
    Cairo Univ, Pharmacognosy Dept, Coll Pharm, Kasr el Aini St,PB 11562, Cairo, Egypt..
    Ali, Sara E.
    German Univ Cairo, Fac Pharm & Biotechnol, Dept Pharmaceut Biol, PB 11835, Cairo, Egypt..
    Hodaya, Rashad H.
    Desert Res Ctr, Plant Prod Dept, PB 11714, Cairo, Egypt..
    El-Seedi, Hesham R.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Avdelningen för farmakognosi. Menoufia Univ, Fac Sci, Dept Chem, Shibin Al Kawm 32512, Egypt..
    Sultani, Haider N.
    Leibniz Inst Plant Biochem, Dept Bioorgan Chem, Weinberg 3, D-06120 Halle, Saale, Germany..
    Laub, Annegret
    Leibniz Inst Plant Biochem, Dept Bioorgan Chem, Weinberg 3, D-06120 Halle, Saale, Germany..
    Eissa, Tarek E.
    Modern Sci & Arts Univ, Coll Pharm, Pharmacognosy Dept, PB 12566, Cairo, Egypt..
    Abou-Zaid, Fouad O. F.
    Desert Res Ctr, Plant Prod Dept, PB 11714, Cairo, Egypt..
    Wessjohann, Ludger A.
    Leibniz Inst Plant Biochem, Dept Bioorgan Chem, Weinberg 3, D-06120 Halle, Saale, Germany..
    Phytochemical Profiles and Antimicrobial Activities of Allium cepa Red cv. and A. sativum Subjected to Different Drying Methods: A Comparative MS-Based Metabolomics2017Inngår i: Molecules, ISSN 1420-3049, E-ISSN 1420-3049, Vol. 22, nr 5, artikkel-id 761Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Plants of the Allium genus produce sulphur compounds that give them a characteristic (alliaceous) flavour and mediate for their medicinal use. In this study, the chemical composition and antimicrobial properties of Allium cepa red cv. and A. sativum in the context of three different drying processes were assessed using metabolomics. Bulbs were dried using either microwave, air drying, or freeze drying and further subjected to chemical analysis of their composition of volatile and non-volatile metabolites. Volatiles were collected using solid phase micro-extraction (SPME) coupled to gas chromatography-mass spectrometry (GC/MS) with 42 identified volatiles including 30 sulphur compounds, four nitriles, three aromatics, and three esters. Profiling of the polar non-volatile metabolites via ultra-performance liquid chromatography coupled to high resolution MS (UPLC/MS) annotated 51 metabolites including dipeptides, flavonoids, phenolic acids, and fatty acids. Major peaks in GC/MS or UPLC/MS contributing to the discrimination between A. sativum and A. cepa red cv. were assigned to sulphur compounds and flavonoids. Whereas sulphur conjugates amounted to the major forms in A. sativum, flavonoids predominated in the chemical composition of A. cepa red cv. With regard to drying impact on Allium metabolites, notable and clear separations among specimens were revealed using principal component analysis (PCA). The PCA scores plot of the UPLC/MS dataset showed closer metabolite composition of microwave dried specimens to freeze dried ones, and distant from air dried bulbs, observed in both A. cepa and A. sativum. Compared to GC/MS, the UPLC/MS derived PCA model was more consistent and better in assessing the impact of drying on Allium metabolism. A phthalate derivative was found exclusively in a commercial garlic preparation via GC/MS, of yet unknown origin. The freeze dried samples of both Allium species exhibited stronger antimicrobial activities compared to dried specimens with A. sativum being in general more active than A. cepa red cv.

  • 16. Irungu, Beatrice N
    et al.
    Orwa, Jennifer A
    Gruhonjic, Amra
    Fitzpatrick, Paul A
    Landberg, Göran
    Kimani, Francis
    Midiwo, Jacob
    Erdelyi, Mate
    Yenesew, Abiy
    Constituents of the roots and leaves of Ekebergia capensis and their potential antiplasmodial and cytotoxic activities.2014Inngår i: Molecules, ISSN 1420-3049, E-ISSN 1420-3049, Vol. 19, nr 9, s. 14235-14246Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    A new triterpenoid, 3-oxo-12β-hydroxy-oleanan-28,13β-olide (1), and six known triterpenoids 2-7 were isolated from the root bark of Ekebergia capensis, an African medicinal plant. A limonoid 8 and two glycoflavonoids 9-10 were found in its leaves. The metabolites were identified by NMR and MS analyses, and their cytotoxicity was evaluated against the mammalian African monkey kidney (vero), mouse breast cancer (4T1), human larynx carcinoma (HEp2) and human breast cancer (MDA-MB-231) cell lines. Out of the isolates, oleanonic acid (2) showed the highest cytotoxicity, i.e., IC50's of 1.4 and 13.3 µM against the HEp2 and 4T1 cells, respectively. Motivated by the higher cytotoxicity of the crude bark extract as compared to the isolates, the interactions of oleanonic acid (2) with five triterpenoids 3-7 were evaluated on vero cells. In an antiplasmodial assay, seven of the metabolites were observed to possess moderate activity against the D6 and W2 strains of P. falciparum (IC50 27.1-97.1 µM), however with a low selectivity index (IC50(vero)/IC50(P. falciparum-D6)<10). The observed moderate antiplasmodial activity may be due to general cytotoxicity of the isolated triterpenoids.

  • 17.
    Jespers, Willem
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för cell- och molekylärbiologi, Beräkningsbiologi och bioinformatik.
    Oliveira, Ana
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för cell- och molekylärbiologi, Beräkningsbiologi och bioinformatik.
    Prieto-Diaz, Ruben
    Univ Santiago Compostela, Fac Farm, Dept Quim Organ, Ctr Singular Invest Quim Biol & Mat Mol CIQUS, Santiago De Compostela 15782, Spain..
    Majellaro, Maria
    Univ Santiago Compostela, Fac Farm, Dept Quim Organ, Ctr Singular Invest Quim Biol & Mat Mol CIQUS, Santiago De Compostela 15782, Spain..
    Åqvist, Johan
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för cell- och molekylärbiologi, Beräkningsbiologi och bioinformatik.
    Sotelo, Eddy
    Univ Santiago Compostela, Fac Farm, Dept Quim Organ, Ctr Singular Invest Quim Biol & Mat Mol CIQUS, Santiago De Compostela 15782, Spain..
    Gutiérrez-de-Terán, Hugo
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för cell- och molekylärbiologi, Beräkningsbiologi och bioinformatik.
    Structure-Based Design of Potent and Selective Ligands at the Four Adenosine Receptors2017Inngår i: Molecules, ISSN 1420-3049, E-ISSN 1420-3049, Vol. 22, nr 11, artikkel-id 1945Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The four receptors that signal for adenosine, A(1), A(2A), A(2B) and A(3) ARs, belong to the superfamily of G protein-coupled receptors (GPCRs). They mediate a number of (patho)physiological functions and have attracted the interest of the biopharmaceutical sector for decades as potential drug targets. The many crystal structures of the A(2A), and lately the A(1) ARs, allow for the use of advanced computational, structure-based ligand design methodologies. Over the last decade, we have assessed the efficient synthesis of novel ligands specifically addressed to each of the four ARs. We herein review and update the results of this program with particular focus on molecular dynamics (MD) and free energy perturbation (FEP) protocols. The first in silico mutagenesis on the A(1)AR here reported allows understanding the specificity and high affinity of the xanthine-antagonist 8-Cyclopentyl-1,3-dipropylxanthine (DPCPX). On the A(2A)AR, we demonstrate how FEP simulations can distinguish the conformational selectivity of a recent series of partial agonists. These novel results are complemented with the revision of the first series of enantiospecific antagonists on the A(2B)AR, and the use of FEP as a tool for bioisosteric design on the A(3)AR.

  • 18.
    Kalepu, Jagadeesh
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Organisk kemi.
    Pilarski, Lukasz T.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Organisk kemi.
    Weinreb Amides as Directing Groups for Transition Metal-Catalyzed C-H Functionalizations2019Inngår i: Molecules, ISSN 1420-3049, E-ISSN 1420-3049, Vol. 24, nr 5, artikkel-id 830Artikkel, forskningsoversikt (Fagfellevurdert)
    Abstract [en]

    Weinreb amides are a privileged, multi-functional group with well-established utility in classical synthesis. Recently, several studies have demonstrated the use of Weinreb amides as interesting substrates in transition metal-catalyzed C-H functionalization reactions. Herein, we review this part of the literature, including the metal catalysts, transformations explored so far and specific insights from mechanistic studies.

  • 19.
    Kang, Naixin
    et al.
    Soochow Univ, Coll Pharmaceut Sci, Dept Pharmacognosy, Suzhou 215123, Peoples R China.
    Shen, Wenhua
    Jiangxi Univ Tradit Chinese Med, Coll Pharmaceut Sci, Nanchang 330006, Jiangxi, Peoples R China.
    Gao, Hongwei
    Guangxi Univ Chinese Med, Coll Pharm, Nanning 530001, Peoples R China.
    Feng, Yulin
    Jiangxi Univ Tradit Chinese Med, Coll Pharmaceut Sci, Nanchang 330006, Jiangxi, Peoples R China.
    Zhu, Weifeng
    Jiangxi Univ Tradit Chinese Med, Coll Pharmaceut Sci, Nanchang 330006, Jiangxi, Peoples R China.
    Yang, Shilin
    Soochow Univ, Coll Pharmaceut Sci, Dept Pharmacognosy, Suzhou 215123, Peoples R China;Jiangxi Univ Tradit Chinese Med, Coll Pharmaceut Sci, Nanchang 330006, Jiangxi, Peoples R China.
    Liu, Yanli
    Soochow Univ, Coll Pharmaceut Sci, Dept Pharmacol, Suzhou 215123, Peoples R China.
    Xu, Qiongming
    Soochow Univ, Coll Pharmaceut Sci, Dept Pharmacognosy, Suzhou 215123, Peoples R China.
    Yu, Di
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Klinisk immunologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Antischistosomal Properties of Hederacolchiside A1 Isolated from Pulsatilla chinensis2018Inngår i: Molecules, ISSN 1420-3049, E-ISSN 1420-3049, Vol. 23, nr 6, artikkel-id 1431Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: Schistosomiasis is a major neglected disease for which the current control strategy involves mass treatment with praziquantel, the only available drug. Hence, there is an urgent need to develop new antischistosomal compounds.

    Methods: The antischistosomal activity of hederacolchiside A1 (HSA) were determined by total or female worm burden reductions in mice harboring Schistosoma japonicum or S. mansoni. Pathology parameters were detected on HSA against 1-day-old S. japonicum-harboring mice. Moreover, we confirmed the antischistosomal effect of HSA on newly transformed schistosomula (NTS) of S. japonicum in vitro.

    Results: HSA, a natural product isolated from Pulsatilla chinensis (Bunge) Regel, was initially corroborated to possess promising antischistosomal properties. We demonstrated that HSA had high activity against S. japonicum and S. mansoni less in 11 days old parasites harbored in mice. The antischistosomal effect was even more than the currently used drugs, praziquantel, and artesunate. Furthermore, HSA could ameliorate the pathology parameters in mice harboring 1-day-old juvenile S. japonicum. We also confirmed that HSA-mediated antischistosomal activity is partly due to the morphological changes in the tegument system when NTS are exposed to HSA.

    Conclusions: HSA may have great potential to be an antischistosomal agent for further research.

  • 20. Klein, Michael
    et al.
    Krainz, Karin
    Redwan, Itedale Namro
    Dinér, Peter
    Department of Chemistry, Medicinal Chemistry, University of Gothenburg.
    Grøtli, Morten
    Synthesis of chiral 1,4-disubstituted-1,2,3-triazole derivatives from amino acids2009Inngår i: Molecules, ISSN 1420-3049, E-ISSN 1420-3049, Vol. 14, nr 12, s. 5124-5143Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    A versatile method for the synthesis of chiral 1,4-disubstituted-1,2,3-triazole derivatives starting from easily accessible naturally occurring D-or L-amino acids as chiral synthons is described. The amino acids were converted into azido alcohols, followed by copper catalyzed [3+2] cycloaddition reactions between the azido alcohols and methyl propiolate and subsequent ester aminolysis with primary and secondary amines furnished the target compounds, which were obtained in excellent yields with no racemization. Docking of selected target compounds shows that the chiral 1,4-disubstituted-1,2,3-triazoles derivatives has the potential of mimicking the binding mode of known purine analogues.

  • 21.
    Martins, Ernane de Freitas
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Fysiska sektionen, Institutionen för fysik och astronomi, Materialteori. Sao Paulo State Univ UNESP, Inst Theoret Phys, Campus Sao Paulo, BR-01140070 Sao Paulo, Brazil;Univ Sao Paulo, Inst Phys, Sao Paulo, SP, Brazil.
    Feliciano, Gustavo Troiano
    Sao Paulo State Univ UNESP, Inst Chem, Campus Araraquara, BR-14800060 Araraquara, Brazil.
    Scheicher, Ralph H.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Fysiska sektionen, Institutionen för fysik och astronomi, Materialteori.
    Rocha, Alexandre Reily
    Sao Paulo State Univ UNESP, Inst Theoret Phys, Campus Sao Paulo, BR-01140070 Sao Paulo, Brazil.
    Simulating DNA Chip Design Using All-Electronic Graphene-Based Substrates2019Inngår i: Molecules, ISSN 1420-3049, E-ISSN 1420-3049, Vol. 24, nr 5, artikkel-id 951Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    In this paper, we present a theoretical investigation of an all-electronic biochip based on graphene to detect DNA including a full dynamical treatment for the environment. Our proposed device design is based on the changes in the electronic transport properties of graphene interacting with DNA strands under the effect of the solvent. To investigate these systems, we applied a hybrid methodology, combining quantum and classical mechanics (QM/MM) coupled to non-equilibrium Green's functions, allowing for the calculations of electronic transport. Our results show that the proposed device has high sensitivity towards the presence of DNA, and, combined with the presence of a specific DNA probe in the form of a single-strand, it presents good selectivity towards specific nucleotide sequences.

  • 22.
    Montero, Jorge
    et al.
    Univ Paris Est, CNRS, UMR 7182, ICMPE,UPEC, F-94320 Thiais, France.
    Zlotea, Claudia
    Univ Paris Est, CNRS, UMR 7182, ICMPE,UPEC, F-94320 Thiais, France.
    Ek, Gustav
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - Ångström, Oorganisk kemi.
    Crivello, Jean-Claude
    Univ Paris Est, CNRS, UMR 7182, ICMPE,UPEC, F-94320 Thiais, France.
    Laversenne, Laetitia
    Univ Grenoble Alpes, CNRS, Grenoble INP, Inst Neel, F-38000 Grenoble, France.
    Sahlberg, Martin
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - Ångström, Oorganisk kemi.
    TiVZrNb Multi-Principal-Element Alloy: Synthesis Optimization, Structural, and Hydrogen Sorption Properties2019Inngår i: Molecules, ISSN 1420-3049, E-ISSN 1420-3049, Vol. 24, nr 15, artikkel-id 2799Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    While the overwhelming number of papers on multi-principal-element alloys (MPEAs) focus on the mechanical and microstructural properties, there has been growing interest in these alloys as solid-state hydrogen stores. We report here the synthesis optimization, the physicochemical and the hydrogen sorption properties of Ti0.325V0.275Zr0.125Nb0.275. This alloy was prepared by two methods, high temperature arc melting and ball milling under Ar, and crystallizes into a single-phase bcc structure. This MPEA shows a single transition from the initial bcc phase to a final bct dihydride and a maximum uptake of 1.7 H/M (2.5 wt%). Interestingly, the bct dihydride phase can be directly obtained by reactive ball milling under hydrogen pressure. The hydrogen desorption properties of the hydrides obtained by hydrogenation of the alloy prepared by arc melting or ball milling and by reactive ball milling have been compared. The best hydrogen sorption properties are shown by the material prepared by reactive ball milling. Despite a fading of the capacity for the first cycles, the reversible capacity of the latter material stabilizes around 2 wt%. To complement the experimental approach, a theoretical investigation combining a random distribution technique and first principle calculation was done to estimate the stability of the hydride.

  • 23.
    Mowbray, Sherry L
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för cell- och molekylärbiologi, Struktur- och molekylärbiologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Kathiravan, Muthu K
    Pandey, Abhishek A
    Odell, Luke R
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Avdelningen för organisk farmaceutisk kemi.
    Inhibition of Glutamine Synthetase: A Potential Drug Target in Mycobacterium tuberculosis2014Inngår i: Molecules, ISSN 1420-3049, E-ISSN 1420-3049, Vol. 19, nr 9, s. 13161-13176Artikkel, forskningsoversikt (Fagfellevurdert)
    Abstract [en]

    Tuberculosis is an infectious disease caused by Mycobacterium tuberculosis. Globally, tuberculosis is second only to AIDS in mortality and the disease is responsible for over 1.3 million deaths each year. The impractically long treatment schedules (generally 6-9 months) and unpleasant side effects of the current drugs often lead to poor patient compliance, which in turn has resulted in the emergence of multi-, extensively- and totally-drug resistant strains. The development of new classes of anti-tuberculosis drugs and new drug targets is of global importance, since attacking the bacterium using multiple strategies provides the best means to prevent resistance. This review presents an overview of the various strategies and compounds utilized to inhibit glutamine synthetase, a promising target for the development of drugs for TB therapy.

  • 24.
    Murugesu, Suganya
    et al.
    Kulliyyah Pharm Int Islamic Univ Malaysia, Dept Pharmaceut Chem, Kuantan 25200, Pahang Darul Ma, Malaysia.
    Ibrahim, Zalikha
    Kulliyyah Pharm Int Islamic Univ Malaysia, Dept Pharmaceut Chem, Kuantan 25200, Pahang Darul Ma, Malaysia.
    Ahmed, Qamar-Uddin
    Kulliyyah Pharm Int Islamic Univ Malaysia, Dept Pharmaceut Chem, Kuantan 25200, Pahang Darul Ma, Malaysia.
    Yusoff, Nik-Idris Nik
    Kulliyyah Pharm Int Islamic Univ Malaysia, Dept Pharmaceut Chem, Kuantan 25200, Pahang Darul Ma, Malaysia.
    Uzir, Bisha-Fathamah
    Kulliyyah Pharm Int Islamic Univ Malaysia, Dept Pharmaceut Chem, Kuantan 25200, Pahang Darul Ma, Malaysia.
    Perumal, Vikneswari
    Univ Kuala Lumpur, Royal Coll Med Perak, Fac Pharm & Hlth Sci, Ipoh 30450, Perak Darul Rid, Malaysia.
    Abas, Faridah
    Univ Putra Malaysia, Lab Nat Prod, Inst Biosci, Serdang 43300, Selangor Darul, Malaysia.
    Saari, Khozirah
    Univ Putra Malaysia, Lab Nat Prod, Inst Biosci, Serdang 43300, Selangor Darul, Malaysia.
    El-Seedi, Hesham
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Farmakognosi. Univ Karachi, HEJ Res Inst Chem, Int Ctr Chem & Biol Sci, Karachi 75270, Pakistan.
    Khatib, Alfi
    Kulliyyah Pharm Int Islamic Univ Malaysia, Dept Pharmaceut Chem, Kuantan 25200, Pahang Darul Ma, Malaysia;Univ Putra Malaysia, Lab Nat Prod, Inst Biosci, Serdang 43300, Selangor Darul, Malaysia.
    Characterization of alpha-Glucosidase Inhibitors from Clinacanthus nutans Lindau Leaves by Gas Chromatography-Mass Spectrometry-Based Metabolomics and Molecular Docking Simulation2018Inngår i: Molecules, ISSN 1420-3049, E-ISSN 1420-3049, Vol. 23, nr 9, artikkel-id 2402Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: Clinacanthus nutans (C. nutans) is an Acanthaceae herbal shrub traditionally consumed to treat various diseases including diabetes in Malaysia. This study was designed to evaluate the alpha-glucosidase inhibitory activity of C. nutans leaves extracts, and to identify the metabolites responsible for the bioactivity. Methods: Crude extract obtained from the dried leaves using 80% methanolic solution was further partitioned using different polarity solvents. The resultant extracts were investigated for their alpha-glucosidase inhibitory potential followed by metabolites profiling using the gas chromatography tandem with mass spectrometry (GC-MS). Results: Multivariate data analysis was developed by correlating the bioactivity, and GC-MS data generated a suitable partial least square (PLS) model resulting in 11 bioactive compounds, namely, palmitic acid, phytol, hexadecanoic acid (methyl ester), 1-monopalmitin, stigmast-5-ene, pentadecanoic acid, heptadecanoic acid, 1-linolenoylglycerol, glycerol monostearate, alpha-tocospiro B, and stigmasterol. In-silico study via molecular docking was carried out using the crystal structure Saccharomyces cerevisiae isomaltase (PDB code: 3A4A). Interactions between the inhibitors and the protein were predicted involving residues, namely LYS156, THR310, PRO312, LEU313, GLU411, and ASN415 with hydrogen bond, while PHE314 and ARG315 with hydrophobic bonding. Conclusion: The study provides informative data on the potential alpha-glucosidase inhibitors identified in C. nutans leaves, indicating the plant's therapeutic effect to manage hyperglycemia.

  • 25.
    Mutulis, Felikss
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för farmaceutisk biovetenskap, Avdelningen för farmaceutisk farmakologi.
    Gogoll, Adolf
    Mutule, Ilze
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för farmaceutisk biovetenskap, Avdelningen för farmaceutisk farmakologi.
    Yahorava, Sviatlana
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för farmaceutisk biovetenskap, Avdelningen för farmaceutisk farmakologi.
    Yahorau, Aleh
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för farmaceutisk biovetenskap, Avdelningen för farmaceutisk farmakologi.
    Liepinsh, Edvards
    Wikberg, Jarl E S
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för farmaceutisk biovetenskap, Avdelningen för farmaceutisk farmakologi.
    Oligomerization of indole derivatives with incorporation of thiols2008Inngår i: Molecules, ISSN 1420-3049, E-ISSN 1420-3049, Vol. 13, nr 8, s. 1846-63Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [ar]

    Two molecules of indole derivative, e.g. indole-5-carboxylic acid, reacted with one molecule of thiol, e.g. 1,2-ethanedithiol, in the presence of trifluoroacetic acid to yield adducts such as 3-[2-(2-amino-5-carboxyphenyl)-1-(2-mercaptoethylthio)ethyl]-1Hindole-5-carboxylic acid. Parallel formation of dimers, such as 2,3-dihydro-1H,1'H-2,3'-biindole-5,5'-dicarboxylic acid and trimers, such as 3,3'-[2-(2-amino-5-carboxyphenyl) ethane-1,1-diyl]bis(1H-indole-5-carboxylic acid) of the indole derivatives was also observed. Reaction of a mixture of indole and indole-5-carboxylic acid with 2-phenylethanethiol proceeded in a regioselective way, affording 3-[2-(2-aminophenyl)-1-(phenethylthio)ethyl]-1H-indole-5-carboxylic acid. An additional product of this reaction was 3-[2-(2-aminophenyl)-1-(phenethylthio)ethyl]-2,3-dihydro-1H,1'H-2,3'-biindole-5'-carboxylic acid, which upon standing in DMSO-d6 solution gave 3-[2-(2-aminophenyl)-1-(phenethylthio)ethyl]-1H,1'H-2,3'-biindole-5'-carboxylic acid. Structures of all compounds were elucidated by NMR, and a mechanism for their formation was suggested.

  • 26. Nichols, Parker J.
    et al.
    Born, Alexandra
    Henen, Morkos A.
    Strotz, Dean
    Orts, Julien
    Olsson, Simon
    Güntert, Peter
    Chi, Celestine N.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk biokemi och mikrobiologi. ETH.
    Vögeli, Beat
    The Exact Nuclear Overhauser Enhancement: Recent Advances2017Inngår i: Molecules, ISSN 1420-3049, E-ISSN 1420-3049, Vol. 22, nr 7, artikkel-id 1176Artikkel, forskningsoversikt (Fagfellevurdert)
    Abstract [en]

    Although often depicted as rigid structures, proteins are highly dynamic systems, whose motions are essential to their functions. Despite this, it is difficult to investigate protein dynamics due to the rapid timescale at which they sample their conformational space, leading most NMR-determined structures to represent only an averaged snapshot of the dynamic picture. While NMR relaxation measurements can help to determine local dynamics, it is difficult to detect translational or concerted motion, and only recently have significant advances been made to make it possible to acquire a more holistic representation of the dynamics and structural landscapes of proteins. Here, we briefly revisit our most recent progress in the theory and use of exact nuclear Overhauser enhancements (eNOEs) for the calculation of structural ensembles that describe their conformational space. New developments are primarily targeted at increasing the number and improving the quality of extracted eNOE distance restraints, such that the multi-state structure calculation can be applied to proteins of higher molecular weights. We then review the implications of the exact NOE to the protein dynamics and function of cyclophilin A and the WW domain of Pin1, and finally discuss our current research and future directions.

  • 27.
    Nyandoro, Stephen S.
    et al.
    Univ Dar Es Salaam, Coll Nat & Appl Sci, Chem Dept, POB 35061, Dar Es Salaam, Tanzania;Univ Gothenburg, Dept Chem & Mol Biol, SE-41296 Gothenburg, Sweden.
    Maeda, Gasper
    Univ Dar Es Salaam, Coll Nat & Appl Sci, Chem Dept, POB 35061, Dar Es Salaam, Tanzania;Univ Gothenburg, Dept Chem & Mol Biol, SE-41296 Gothenburg, Sweden.
    Munissi, Joan J. E.
    Univ Dar Es Salaam, Coll Nat & Appl Sci, Chem Dept, POB 35061, Dar Es Salaam, Tanzania.
    Gruhonjic, Amra
    Univ Gothenburg, Dept Chem & Mol Biol, SE-41296 Gothenburg, Sweden.
    Fitzpatrick, Paul A.
    Univ Gothenburg, Sahlgrenska Canc Ctr, SE-40530 Gothenburg, Sweden.
    Lindblad, Sofia
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Organisk kemi.
    Duffy, Sandra
    Griffith Univ, Griffith Inst Drug Discovery, Discovery Biol, Nathan, Qld 4111, Australia.
    Pelletier, Jerry
    McGill Univ, Dept Biochem, Montreal, PQ H3G 1Y6, Canada.
    Pan, Fangfang
    Cent China Normal Univ, Hubei Int Sci & Technol Cooperat Base Pesticide &, Coll Chem, Key Lab Pesticide & Chem Biol,Minist Educ, Luoyu Rd 152, Wuhan 430079, Hubei, Peoples R China;Univ Jyvaskyla, Dept Chem, POB 35, FI-40014 Jyvaskyla, Finland.
    Puttreddy, Rakesh
    Univ Jyvaskyla, Dept Chem, POB 35, FI-40014 Jyvaskyla, Finland.
    Avery, Vicky M.
    Griffith Univ, Griffith Inst Drug Discovery, Discovery Biol, Nathan, Qld 4111, Australia.
    Erdélyi, Máté
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Organisk kemi. Univ Gothenburg, Dept Chem & Mol Biol, SE-41296 Gothenburg, Sweden;.
    A New Benzopyranyl Cadenane Sesquiterpene and Other Antiplasmodial and Cytotoxic Metabolites from Cleistochlamys kirkii2019Inngår i: Molecules, ISSN 1420-3049, E-ISSN 1420-3049, Vol. 24, nr 15, artikkel-id 2746Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Phytochemical investigations of ethanol root bark and stem bark extracts of Cleistochlamys kirkii (Benth.) Oliv. (Annonaceae) yielded a new benzopyranyl cadinane-type sesquiterpene (cleistonol, 1) alongside 12 known compounds (2-13). The structures of the isolated compounds were established from NMR spectroscopic and mass spectrometric analyses. Structures of compounds 5 and 10 were further confirmed by single crystal X-ray crystallographic analyses, which also established their absolute stereochemical configuration. The ethanolic crude extract of C. kirkii root bark gave 72% inhibition against the chloroquine-sensitive 3D7-strain malaria parasite Plasmodium falciparum at 0.01 mu g/mL. The isolated metabolites dichamanetin, (E)-acetylmelodorinol, and cleistenolide showed IC50 = 9.3, 7.6 and 15.2 mu M, respectively, against P. falciparum 3D7. Both the crude extract and the isolated compounds exhibited cytotoxicity against the triple-negative, aggressive breast cancer cell line, MDA-MB-231, with IC50 = 42.0 mu g/mL (crude extract) and 9.6-30.7 mu M (isolated compounds). Our findings demonstrate the potential applicability of C. kirkii as a source of antimalarial and anticancer agents.