Design, synthesis and<i>in vitro</i>antiproliferative activity of new thiazolidinedione-1,3,4-oxadiazole hybrids as thymidylate synthase inhibitors

Abstract

Thymidylate synthase (TS) has been an attention-grabbing area of research for the treatment of cancers due to their role in DNA biosynthesis. In the present study, we have synthesised a library of thiazolidinedione-1,3,4-oxadiazole hybrids as TS inhibitors. All the synthesised hybrids followed Lipinski and Veber rules which indicated good drug likeness properties upon oral administration. Among the synthesised hybrids, compound <b>9</b> and <b>10</b> displayed 4.5 and 4.4 folds activity of 5-Fluorouracil, respectively against MCF-7 cell line whereas 3.1 and 2.5 folds cytotoxicity against HCT-116 cell line. Furthermore, compound <b>9</b> and <b>10</b> also inhibited TS enzyme with IC₅₀ = 1.67 and 2.21 µM, respectively. Finally, the docking studies of <b>9</b> and <b>10</b> were found to be consistent with <i>in vitro</i> TS results. From these studies, compound <b>9</b> and <b>10</b> has the potential to be developed as TS inhibitors.