Synthesis and structure-activity relationships of harmine derivatives as potential antitumor agents.

Rihui Cao, Wenxi Fan, Liang Guo, Qin Ma, Guoxian Zhang, Jianru Li, Xuemei Chen, Zhenghua Ren, Liqin Qiu

School of Chemistry and Chemical Engineering, Sun Yat-sen University, 135 Xin Gang Xi Road, Guangzhou 510275, PR China. caorihui@mail.sysu.edu.cn

European journal of medicinal chemistry 2013 Feb

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Harmine, a naturally occurring β-carboline alkaloid, showed good antitumor activities together with remarkable neurotoxic effects in animal models. In order to search for novel leading compounds endowed with better antitumor activities and less neurotoxicities, a series of harmine derivatives were designed and synthesized by modification of position-2, 7 and 9 of β-carboline nucleus, and their cytotoxic activities against human tumor cell lines were investigated. Acute toxicities and antitumor activities of the selected compounds in mice were also evaluated. Structure-activity relationships studies confirmed that (1) the 7-methoxy structural moiety was the pharmacophore responsible for the neurotoxic effects of this class of compounds; (2) the substituents in position-2 and 9 played a vital role in modulation of their antitumor activities. Copyright © 2012 Elsevier Masson SAS. All rights reserved.

Citation

Rihui Cao, Wenxi Fan, Liang Guo, Qin Ma, Guoxian Zhang, Jianru Li, Xuemei Chen, Zhenghua Ren, Liqin Qiu. Synthesis and structure-activity relationships of harmine derivatives as potential antitumor agents. European journal of medicinal chemistry. 2013 Feb;60:135-43