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 IC₅₀ = 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.

摘要

胸苷酸合酶（TS）由于其在DNA生物合成中的作用而成为治疗癌症的研究热点。在本研究中，我们已经合成了噻唑烷二酮-1,3,4-恶二唑杂合体作为TS抑制剂的库。所有合成的杂种均遵循Lipinski和Veber规则，这表明口服给药时具有良好的药物相似性。在合成的杂种中，化合物9和10分别显示出5-氟尿嘧啶对MCF-7细胞系的4.5和4.4倍活性，而对HCT-116细胞系的细胞毒性是3.1和2.5倍。此外，化合物9和10还通过IC ₅₀抑制TS酶分别为1.67和2.21 µM。最后，发现9和10的对接研究与体外TS结果一致。根据这些研究，化合物9和10有可能被开发为TS抑制剂。