Synthesis and biological evaluation of N9-substituted harmine derivatives as potential anticancer agents. Issue 16 (15th August 2016)

• Record Type: Journal Article
• Authors: Du, Hongtao; Tian, Shan; Chen, Juncheng; Gu, Hongling; Li, Na; Wang, Junru
• Is Part Of: Bioorganic & medicinal chemistry letters. Volume 26:Issue 16(2016)
• Page Start: 4015
• Page End: 4019
• Publication Date: 2016-08-15
• Subjects: Harmine derivatives -- Anticancer activities -- Structure–activity relationships (SARs) -- Apoptosis -- Cell cycle arrest; Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; 572
• DOI: 10.1016/j.bmcl.2016.06.087
• Languages: English
• ISSNs: 0960-894X

Abstract

Graphical abstract: Abstract: A series of N 9 -substituted harmine derivatives were synthesized and evaluated for their anticancer activity on a panel of cancer cell lines, their apoptosis induction and their cell cycle effects. The results showed that N 9 -substituted harmine derivatives had anticancer effects. In particular, N 9 -haloalkyl derivatives9a –9c and N 9 -acyl harmine derivatives11c and11d, with IC50 values less than 1 μM, were more potent than doxorubicin against A-549 and/or MCF-7 cell lines. Moreover, structure–activity relationships (SARs) indicated that introducing a haloalkyl or benzenesulfonyl group in the N 9 -position of harmine could significantly increase the anticancer activity. The most active compound (11d ) caused cell cycle arrest in the G2/M phase, and induced cell apoptosis in a dose-dependent manner.