Design,synthesis and antitumour and anti-angiogenesis evaluation of 22 moscatilin derivatives |
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| Affiliation: | 1. Department of Natural Medicinal Chemistry, China Pharmaceutical University, Nanjing 210009, China;2. Institute of Translational Medicine, College of Biotechnology and Pharmaceutical Engineering, Nanjing Tech University, Nanjing 211800, China;3. Department of Pharmaceutical Analysis, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing 210009, China;4. Key Laboratory of Drug Quality Control and Pharmacovigilance (China Pharmaceutical University), Ministry of Education, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing 210009, China;5. Key Laboratory of Biomedical Functional Materials, China Pharmaceutical University, Nanjing 211198, China;6. State Key Laboratory of Innovative Natural Medicines and TCM Injections, Jiangxi Qingfeng Pharmaceutical Co., Ltd., Ganzhou 341000, Jiangxi, China |
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| Abstract: | Two series of moscatilin derivatives were designed, synthesized and evaluated as anti-tumor and anti-angiogenesis agents. Most of these compounds showed moderate-to-obvious cytotoxicity against five cancer cell lines (A549, HepG2, MDA-MB-231, MKN-45, HCT116). Among these cell lines, compounds had obvious effects on HCT116. Especially for 8Ae, the IC50 was low to 0.25 μM. 8Ae can inhibit the viability and induce the apoptosis of HCT116 cells but exhibit no cytotoxic activity in noncancerous NCM460 colon cells. 8Ae can also arrest the G2/M cell cycle in HCT116 cells by inhibiting the α-tubulin expression. Zebrafish bioassay-guided screen showed the 22 moscatilin derivatives had potent anti-angiogenic activities and compound 8Ae had better activities than positive compound. Molecular docking indicated 8Ae interacted with tubulin at the affinity of −7.2 Kcal/mol. In conclusion, compound 8Ae was a potential antitumor and anti-angiogenesis candidate for further development. |
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| Keywords: | Antitumor Anti-angiogenesis Bibenzyl Moscatilin derivatives Tubulin |
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