新型噻唑烷二酮-1,3,4-噁二唑杂合作为胸苷酸合成酶抑制剂的设计、合成及抗增殖活性。
Design, synthesis and antiproliferative activity of new thiazolidinedione-1,3,4-oxadiazole hybrids as thymidylate synthase inhibitors.
机构信息
Department of Chemistry, Faculty of Science, Albaha University, Albaha, Saudi Arabia.
Department of Pharmacology and Toxicology, Faculty of Pharmacy, King Abdulaziz University, Jeddah, Saudi Arabia.
出版信息
J Enzyme Inhib Med Chem. 2020 Dec;35(1):1116-1123. doi: 10.1080/14756366.2020.1759581.
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 and 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 and also inhibited TS enzyme with IC = 1.67 and 2.21 µM, respectively. Finally, the docking studies of and were found to be consistent with TS results. From these studies, compound and has the potential to be developed as TS inhibitors.
胸苷酸合成酶（TS）在 DNA 生物合成中发挥作用，因此一直是癌症治疗研究的热点。在本研究中，我们合成了一系列噻唑烷二酮-1,3,4-恶二唑杂合体作为 TS 抑制剂。所有合成的杂合体均遵循 Lipinski 和 Veber 规则，这表明口服给药时具有良好的药物相似性。在所合成的杂合体中，化合物 和 对 MCF-7 细胞系的活性分别是 5-氟尿嘧啶的 4.5 和 4.4 倍，而对 HCT-116 细胞系的细胞毒性分别是 3.1 和 2.5 倍。此外，化合物 和 对 TS 酶的抑制作用也分别为 IC = 1.67 和 2.21 μM。最后，化合物 和 的对接研究结果与 TS 结果一致。从这些研究中可以看出，化合物 和 有潜力被开发为 TS 抑制剂。
Zotero 插件