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
9
and
10
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
9
and
10
also inhibited TS enzyme with IC
50
= 1.67 and 2.21 µM, respectively. Finally, the docking studies of
9
and
10
were found to be consistent with
in vitro
TS results. From these studies, compound
9
and
10
has the potential to be developed as TS inhibitors.