Synthesis and biological evaluation of N9-substituted harmine derivatives as potential anticancer agents

A series of N9-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 N9-substituted harmine derivatives had anticancer effects. In particular, N9-haloalkyl derivatives 9a–9c and N9-acyl harmine derivatives 11c and 11d, 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 N9-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.

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