Synthesis of panaxadiol thiadiazole derivatives and study on its potential cell cycle arrest

• Published in: Journal of molecular structure Vol. 1264; p. 133208
• Main Authors: Dai, Rongke, Li, Tao, Xiao, Shengnan, Chen, Yu, Gao, Jiaming, Su, Guangyue, Zhao, Yuqing
• Format: Journal Article
• Language: English
• Published: Elsevier B.V 15.09.2022
• Subjects: Activity; Docking; Panaxadiol; Synthesis; Thiadiazole; Activity; Docking; Synthesis; Panaxadiol; Thiadiazole
• ISSN: 0022-2860; 1872-8014
• DOI: 10.1016/j.molstruc.2022.133208

•A series of new panaxadiol thiadiazole derivatives were designed and synthesized.•Compound SP24 significantly inhibited the growth of various tumor cells.•Compound SP24 could block the cell cycle in G1/S-phase.•A docking study was performed on the known structures of CDK2 and CDK6. In this study, panaxadiol (PD) derivatives were designed and synthesized by the reaction of thiadiazoles with PD. The identity of all final products was elucidated by 1H, 13C NMR, HR-MS. The cytotoxicity activities of the derivatives were evaluated against four cancer cell lines using the MTT assay which revealed they indicated excellent anticancer activity. Among these compounds, SP24 had the most significant cytotoxicity and distinctly inhibited the growth of a variety of tumor cells. Further studies showed that compound SP24 could decrease the expression levels of CDKs protein family and Cyclin D1 in A549, suggesting that compound SP24 could block the cell cycle. To prove the above conclusions, we simulated the binding sites of the two proteins by molecular docking method. The results demonstrated that the docking scores of SP24 and the two cyclins are higher than that of PD. Based on the complex of the target protein and ligand, we speculate that the enhanced antiproliferative activity may be related to the increased hydrogen bonding interactions. Therefore, these data provide a reference that compound SP24 could be a promising lead drug for cancer treatment. [Display omitted]