uu.seUppsala University Publications
Change search
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
Substitution of the phosphonic acid and hydroxamic acid functionalities of the DXR inhibitor FR900098: An attempt to improve the activity against Mycobacterium tuberculosis
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Organic Pharmaceutical Chemistry.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Organic Pharmaceutical Chemistry.ORCID iD: 0000-0002-4420-772X
Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, Structure and Molecular Biology.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Organic Pharmaceutical Chemistry.
Show others and affiliations
2011 (English)In: Bioorganic & Medicinal Chemistry Letters, ISSN 0960-894X, E-ISSN 1090-2120, Vol. 21, no 18, 5403-5407 p.Article in journal (Refereed) Published
Abstract [en]

Two series of FR900098/fosmidomycin analogs were synthesized and evaluated for MtDXR inhibition and Mycobacterium tuberculosis whole-cell activity. The design rationale of these compounds involved the exchange of either the phosphonic acid or the hydroxamic acid part for alternative acidic and metal-coordinating functionalities. The best inhibitors provided IC(50) values in the micromolar range, with a best value of 41 mu M.

Place, publisher, year, edition, pages
2011. Vol. 21, no 18, 5403-5407 p.
Keyword [en]
Tuberculosis, DXR, Enzyme inhibitor, Fosmidomycin, FR900098
National Category
Chemical Sciences
Identifiers
URN: urn:nbn:se:uu:diva-158288DOI: 10.1016/j.bmcl.2011.07.005ISI: 000294051800057OAI: oai:DiVA.org:uu-158288DiVA: diva2:439403
Available from: 2011-09-07 Created: 2011-09-06 Last updated: 2017-12-08
In thesis
1. Computational Modelling in Drug Discovery: Application of Structure-Based Drug Design, Conformal Prediction and Evaluation of Virtual Screening
Open this publication in new window or tab >>Computational Modelling in Drug Discovery: Application of Structure-Based Drug Design, Conformal Prediction and Evaluation of Virtual Screening
2017 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Structure-based drug design and virtual screening are areas of computational medicinal chemistry that use 3D models of target proteins. It is important to develop better methods in this field with the aim of increasing the speed and quality of early stage drug discovery.

The first part of this thesis focuses on the application of structure-based drug design in the search for inhibitors for the protein 1-deoxy-D-xylulose-5-phosphate reductoisomerase (DXR), one of the enzymes in the DOXP/MEP synthetic pathway. This pathway is found in many bacteria (such as Mycobacterium tuberculosis) and in the parasite Plasmodium falciparum.

In order to evaluate and improve current virtual screening methods, a benchmarking data set was constructed using publically available high-throughput screening data. The exercise highlighted a number of problems with current data sets as well as with the use of publically available high-throughput screening data. We hope this work will help guide further development of well designed benchmarking data sets for virtual screening methods.

Conformal prediction is a new method in the computer-aided drug design toolbox that gives the prediction range at a specified level of confidence for each compound. To demonstrate the versatility and applicability of this method we derived models of skin permeability using two different machine learning methods; random forest and support vector machines.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2017. 47 p.
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Pharmacy, ISSN 1651-6192 ; 235
Keyword
drug discovery, docking, virtual screening, tuberculosis, conformal prediction
National Category
Medicinal Chemistry
Identifiers
urn:nbn:se:uu:diva-328505 (URN)978-91-513-0049-8 (ISBN)
Public defence
2017-10-13, B/B42, Husargatan 3, Uppsala, 09:00 (English)
Opponent
Supervisors
Available from: 2017-09-21 Created: 2017-08-24 Last updated: 2017-10-17

Open Access in DiVA

No full text

Other links

Publisher's full text

Authority records BETA

Lindh, MartinKarlén, AndersLarhed, Mats

Search in DiVA

By author/editor
Lindh, MartinKarlén, AndersLarhed, Mats
By organisation
Organic Pharmaceutical ChemistryStructure and Molecular Biology
In the same journal
Bioorganic & Medicinal Chemistry Letters
Chemical Sciences

Search outside of DiVA

GoogleGoogle Scholar

doi
urn-nbn

Altmetric score

doi
urn-nbn
Total: 580 hits
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf