Inhibitor of Ovarian Cancer Cells Growth by Virtual Screening: A New Thiazole Derivative Targeting Human Thymidylate Synthase

Journal of Medicinal Chemistry
2012.0

Abstract

Human thymidylate synthase (hTS) was targeted through a virtual screening approach. The most optimal inhibitor identified, 2-{4-hydroxy-2-[(2-hydroxybenzylidene)hydrazono]-2,5-dihydrothiazol-5-yl}-N-(3-trifluoromethylphenyl)acetamide (5), showed a mixed-type inhibition pattern, with a K(i) of 1.3 μM and activity against ovarian cancer cell lines with the same potency as cisplatin. X-ray studies revealed that it binds the inactive enzyme conformation. This study is the first example of a nonpeptidic inhibitor that binds the inactive hTS and exhibits anticancer activity against ovarian cancer cells.

Knowledge Graph

Similar Paper

Inhibitor of Ovarian Cancer Cells Growth by Virtual Screening: A New Thiazole Derivative Targeting Human Thymidylate Synthase
Journal of Medicinal Chemistry 2012.0
Optimization of Peptides That Target Human Thymidylate Synthase to Inhibit Ovarian Cancer Cell Growth
Journal of Medicinal Chemistry 2014.0
Identification of a novel class of inhibitor of human and Escherichia coli thymidine phosphorylase by in silico screening
Bioorganic & Medicinal Chemistry Letters 2003.0
Novel 1,3,4-oxadiazole thioether derivatives targeting thymidylate synthase as dual anticancer/antimicrobial agents
Bioorganic & Medicinal Chemistry 2013.0
Design, synthesis and evaluation of thiohydantoin derivatives as potent topoisomerase I (Top1) inhibitors with anticancer activity
European Journal of Medicinal Chemistry 2015.0
Design, synthesis and evaluation of 4-substituted anthra[2,1-c][1,2,5]thiadiazole-6,11-dione derivatives as novel non-camptothecin topoisomerase I inhibitors
Bioorganic & Medicinal Chemistry Letters 2017.0
Synthesis, biological evaluation, and molecular docking studies of 1,3,4-thiadiazol-2-amide derivatives as novel anticancer agents
Bioorganic & Medicinal Chemistry 2012.0
Development of thiazole-appended novel hydrazones as a new class of α-amylase inhibitors with anticancer assets: anin silicoandin vitroapproach
RSC Medicinal Chemistry 2023.0
A potent multisubstrate analog inhibitor of human thymidylate synthetase
Journal of Medicinal Chemistry 1984.0
Synthesis and evaluation of 2-[2-(phenylthiomethyl)-1H-benzo[d] imidazol-1-yl)acetohydrazide derivatives as antitumor agents
Bioorganic & Medicinal Chemistry Letters 2012.0