Design, synthesis and QSAR study of novel isatin analogues inspired Michael acceptor as potential anticancer compounds

• Published in: European journal of medicinal chemistry 2018-01, Vol.144, p.493-503
• Main Authors: Wang, Jiabing, Yun, Di, Yao, Jiali, Fu, Weitao, Huang, Fangyan, Chen, Liping, Wei, Tao, Yu, Cuijuan, Xu, Haineng, Zhou, Xiaoou, Huang, Yanqing, Wu, Jianzhang, Qiu, Peihong, Li, Wulan
• Format: Article
• Language: English
• Subjects: Anticancer; Association principle; Chemotherapeutics; Quantitative structure-activity relationship
• ISSN: 0223-5234; 1768-3254
• DOI: 10.1016/j.ejmech.2017.12.043

Molecular hybridization is considered as an effective tactic to develop drugs for the treatment of cancer. A series of novel hybrid compounds of isatin and Michael acceptor were designed and synthesized on the basis of association principle. These hybrid compounds were tested for cytotoxic potential against human cancer cell lines namely, BGC-823, SGC-7901 and NCI-H460 by MTT assay. Most compounds showed good anti-growth activities in all tested human cancer cells. SAR and QSAR analysis may provide vital information for the future development of novel anti-cancer inhibitors. Notably, compound 6a showed potent growth inhibition on BGC-823, SGC-7901 and NCI-H460 with the IC50 values of 3.6 ± 0.6, 5.7 ± 1.2, 3.2 ± 0.7 μM, respectively. Besides, colony formation assays, wound healing assays and flow cytometry analysis indicated 6a exhibited a potent anti-growth and anti-migration ability in a concentration-dependence manner through arrested cells in the G2/M phase of cell cycle. Moreover, 6a significantly repressed tumor growth in a NCI-H460 xenograft mouse model. Overall, our findings suggested isatin analogues inspired Michael acceptor may provide promising lead compounds for the development of cancer chemotherapeutics. [Display omitted] •A series of novel isatin analogues inspired Michael acceptor were designed and synthesized based on association principle.•Most analogues showed good anticancer activity and QSAR model was constructed to investigate these analogues.•6a significantly inhibited NCI-H460 cells growth in vitro and in vivo, which showed more remarkable activity than curcumin.