Design, synthesis and in vitro antiproliferative activity of new thiazolidinedione-1, 3, 4-oxadiazole hybrids as thymidylate synthase inhibitors. (1st January 2020)

• Record Type: Journal Article
• Authors: Alzhrani, Zohor Mohammad Mahdi; Alam, Mohammad Mahboob; Neamatallah, Thikryat; Nazreen, Syed
• Is Part Of: Journal of enzyme inhibition and medicinal chemistry. Volume 35:Number 1(2020)
• Page Start: 1116
• Page End: 1123
• Publication Date: 2020-01-01
• Subjects: 2, 4-thiazolidinediones -- 1, 3, 4-oxadiazoles -- thymidylate synthase -- molecular docking -- pharmacokinetics; Enzyme inhibitors -- Periodicals; Enzyme Inhibitors -- periodicals; Biochemistry -- periodicals; 572.7
• DOI: 10.1080/14756366.2020.1759581
• Languages: English
• ISSNs: 1475-6366

Abstract

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.