Synthesis and characterisation of celastrol derivatives as potential anticancer agents

Journal of Enzyme Inhibition and Medicinal Chemistry

Zhe-Shan Quan¹  Hong-Jian Zhang¹  Hu-Ri Piao¹  Guo-Rui Zhang¹ 

[1] Key Laboratory of Natural Resources and Functional Molecules of the Changbai Mountain, Affiliated Ministry of Education, College of Pharmacy, Yanbian University, Yanji, Jilin, Chin;

关键词: Synthesis;    celastrol;    amino acid;    triazole;    anticancer;    docking;   

DOI  :  10.1080/14756366.2017.1404590

来源: publisher

【 摘 要 】

In the present study, three series of novel celastrol derivatives were designed and synthesised by modifying the carboxylic acid at the 20th position with amino acid, amine, and triazole derivatives. All the synthesised compounds were screened for their anticancer activities using MTT assay against AGS, MGC-803, SGC-7901, HCT-116, A549, HeLa, BEL-7402, and HepG-2 cell lines. Most of the synthesised compounds exhibited potent antiproliferative effects. The most promising compound 3-Hydroxy-9β,13α-dimethyl-2-oxo-24,25,26-trinoroleana-1(10),3,5,7-tetraen-29-oic amide, N-(R)-methyl-3-(1H-indol-2-yl)propanoate (11) showed considerable high anticancer activity against AGS cell lines, with an IC50 value of 0.44 μM, and considerably higher activities against HCT-116, BEL-7402, and HepG-2 cell lines, with IC50 values of 0.78, 0.63, and 0.76 μM, respectively. The results of apoptosis tests and molecular docking study of compound 11 binding to Caspase-3 revealed that its mechanism of action with antiproliferative was possibly involved in inducing apoptosis by inducing the activation of caspase-3.

【 授权许可】

CC BY