2. Academic Validation
  3. Design, synthesis and antitumour and anti-angiogenesis evaluation of 22 moscatilin derivatives

Design, synthesis and antitumour and anti-angiogenesis evaluation of 22 moscatilin derivatives

  • Bioorg Med Chem. 2019 Jun 15;27(12):2657-2665. doi: 10.1016/j.bmc.2019.04.027.
Li Guan 1,  Junting Zhou 2,  Qinghua Lin 2,  Huilin Zhu 2,  Wenyuan Liu 3,  Baolin Liu 4,  Yanbo Zhang 5,  Jie Zhang 2,  Jing Gao 6,  Feng Feng 7,  Wei Qu 8
Affiliations

Affiliations

  • 1 Department of Natural Medicinal Chemistry, China Pharmaceutical University, Nanjing 210009, China; Institute of Medicine, Xi'an Medical University, Xi'an 710021, China.
  • 2 Department of Natural Medicinal Chemistry, China Pharmaceutical University, Nanjing 210009, China.
  • 3 Key Laboratory of Drug Quality Control and Pharmacovigilance (China Pharmaceutical University), Ministry of Education, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing 210009, China.
  • 4 Department of Pharmacology of Chinese Materia Medica, China Pharmaceutical University, Nanjing 210009, China.
  • 5 School of Chinese Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China.
  • 6 The Joint Laboratory of Chinese Pharmaceutical University and Taian City Centrol Hopspital, Taian City Centrol Hospitol, Taian 271000, China.
  • 7 Department of Natural Medicinal Chemistry, China Pharmaceutical University, Nanjing 210009, China; Key Laboratory of Biomedical Functional Materials, China Pharmaceutical University, Nanjing 211198, China; Jiang Su Food and Pharmaceutical Science College, huai'an 223003, China. Electronic address: fengfeng@cpu.edu.cn.
  • 8 Department of Natural Medicinal Chemistry, China Pharmaceutical University, Nanjing 210009, China; Key Laboratory of Biomedical Functional Materials, China Pharmaceutical University, Nanjing 211198, China. Electronic address: popoqzh@126.com.
PMID: 31047774 DOI: 10.1016/j.bmc.2019.04.027
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.

Keywords

Anti-angiogenesis; Antitumor; Bibenzyl; Moscatilin derivatives; Tubulin.

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