Design, synthesis and QSAR study of novel isatin analogues inspired Michael acceptor as potential anticancer compounds
| Autor: | Tao Wei, Wulan Li, Jiali Yao, Jianzhang Wu, Di Yun, Cuijuan Yu, Haineng Xu, Xiaoou Zhou, Peihong Qiu, Yanqing Huang, Liping Chen, Fangyan Huang, Jiabing Wang, Weitao Fu |
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| Rok vydání: | 2018 |
| Předmět: |
Isatin
Quantitative structure–activity relationship Mice Nude Quantitative Structure-Activity Relationship Antineoplastic Agents 01 natural sciences Flow cytometry Mice 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Drug Discovery Tumor Cells Cultured medicine Animals Humans MTT assay Cell Proliferation Pharmacology Mice Inbred BALB C Dose-Response Relationship Drug Molecular Structure medicine.diagnostic_test 010405 organic chemistry Organic Chemistry Neoplasms Experimental General Medicine Cell cycle 0104 chemical sciences Biochemistry chemistry Cell culture Drug Design 030220 oncology & carcinogenesis Michael reaction Drug Screening Assays Antitumor Growth inhibition |
| Zdroj: | European Journal of Medicinal Chemistry. 144:493-503 |
| ISSN: | 0223-5234 |
| DOI: | 10.1016/j.ejmech.2017.12.043 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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