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

Human Thymidylate Synthase (hTS) was targeted through a virtual screening approach. The most optimal inhibitor identified, 2-{4-hydroxy-2-[(2-hydroxy-benzylidene)-hydrazono]-2,5-dihydro-thiazol-5-yl}-N-(3-trifluoromethyl-phenyl)-acetamide (5), showed a mixed-type inhibition pattern. The inhibitor exhibited a Ki of 1.3 µM and was active against four ovarian cancer cell lines with the same potency as cisplatin. The co-crystal structure with hTS revealed that the inhibitor binds the inactive enzyme conformation. This study is the first example of a non-peptidic inhibitor that binds the inactive hTS and exhibits anticancer activity against ovarian cancer cells.