Journal
BIOORGANIC & MEDICINAL CHEMISTRY
Volume 27, Issue 12, Pages 2657-2665Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.bmc.2019.04.027
Keywords
Antitumor; Anti-angiogenesis; Bibenzyl; Moscatilin derivatives; Tubulin
Funding
- National Natural Science Foundation of China [81373956, 81274064, 81502950, 81573557]
- Seed Funding Program for Basic Research from HKU [201111159043]
- Priority Academic Program Development of Jiangsu Higher Education Institutions
- Fundamental Research Funds for the Central Universities [2015ZD010]
- Huahai Graduate Innovation Fund [CX14B-007HH]
- College Students Innovation Project for the R&D of Novel Drugs [J1030830]
- Xi'an Medical University Ph.D. Research Startup Fund Project [2017DOC06]
- China pharmaceutical university
- Taian city central hospital
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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 mu M. 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 alpha-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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