Inhibitor of ovarian cancer cells growth by virtual screening: a new thiazole derivative targeting human thymidylate synthase

J Med Chem. 2012 Nov 26;55(22):10272-6. doi: 10.1021/jm300850v.

Emanuele Carosati ¹, Anna Tochowicz, Gaetano Marverti, Giambattista Guaitoli, Paolo Benedetti, Stefania Ferrari, Robert M Stroud, Janet Finer-Moore, Rosaria Luciani, Davide Farina, Gabriele Cruciani, M Paola Costi

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Affiliation

1 Dipartimento di Chimica, Università degli Studi di Perugia , Via Elce di Sotto 10, 06123, Perugia, Italy.

PMID: 23075414 DOI: 10.1021/jm300850v

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.

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