Design, synthesis and antitumour and anti-angiogenesis evaluation of 22 moscatilin derivatives. Issue 12 (15th June 2019)

• Record Type: Journal Article
• Authors: Guan, Li; Zhou, Junting; Lin, Qinghua; Zhu, Huilin; Liu, Wenyuan; Liu, Baolin; Zhang, Yanbo; Zhang, Jie; Gao, Jing; Feng, Feng; Qu, Wei
• Is Part Of: Bioorganic & medicinal chemistry. Volume 27:Issue 12(2019)
• Page Start: 2657
• Page End: 2665
• Publication Date: 2019-06-15
• Subjects: Antitumor -- Anti-angiogenesis -- Bibenzyl -- Moscatilin derivatives -- Tubulin; Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; Biochemistry -- Periodicals; Chemistry, Clinical -- Periodicals; Chemistry, Organic -- Periodicals; Chimie bio-organique -- Périodiques; Chimie pharmaceutique -- Périodiques; 615.19
• DOI: 10.1016/j.bmc.2019.04.027
• Languages: English
• ISSNs: 0968-0896

Abstract

Graphical abstract: Highlights: Two series of moscatilin derivatives were designed, synthesized and evaluated as anti-tumor and anti-angiogenesis agents. 8Ae can inhibit the viability and induce the apoptosis of HCT116 cells. 8Ae could arrest G2–M cell-cycle by inhibiting α-tubulin expression. Zebrafish bioassay-guided screen showed compound8Ae had better anti-angiogenic activities than positive compound. 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 for8Ae, 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 compound8Ae had better activities than positive compound. Molecular docking indicated 8Ae interacted with tubulin at the affinity of −7.2 Kcal/mol. In conclusion, compound8Ae was a potential antitumor and anti-angiogenesis candidate for further development.