Newly Designed and Synthesized Curcumin Analogs with in vitro Cytotoxicity and Tubulin Polymerization Activity
2015 (English)In: Chemical Biology and Drug Design, ISSN 1747-0277, Vol. 86, no 1, 860-870 p.Article in journal (Refereed) Published
Novel curcumin analogs with 4-piperidone ring were designed, synthesized, and evaluated for their cytotoxic activities against five different cancer cell lines. 3,5-bis(4-Hydroxy-3-methoxybenzylidene)-4-oxo-N-phenylpiperidine-1-carbothioamide (XIIe) exhibited considerable cytotoxic activity with IC50 values in 1-2.5m range. In silico and in vitro, studies were also performed to predict the binding affinity of the target compounds to the -chain of tubulin receptor (PDB code 1SA1) and their abilities to affect microtubules polymerization cycle. 3,5-bis(3-Iodo-5-methoxy-4-propoxybenzylidene)-N-acetylpiperidin-4-one (VIIa) was found to exert 93.3% inhibition of tubulin and destabilization of microtubules in vitro compared to vincristine while, 3,5-bis(3,4,5-trimethoxybenzylidene)-N-benzoylpiperidin-4-one (XIIc) showed high potency in a differentway where it exerted 94.8% stabilization of microtubules in vitro compared to positive control paclitaxel.
Place, publisher, year, edition, pages
2015. Vol. 86, no 1, 860-870 p.
curcumin analogs, cytotoxicity, molecular modeling, tubulin polymerization assay
Pharmacology and Toxicology
IdentifiersURN: urn:nbn:se:uu:diva-257623DOI: 10.1111/cbdd.12464ISI: 000356362300005PubMedID: 25352318OAI: oai:DiVA.org:uu-257623DiVA: diva2:841026