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HERO ID
5972295
Reference Type
Journal Article
Title
Design, synthesis and in vitro and in vivo antitumor activities of novel beta-carboline derivatives
Author(s)
Cao, R; Chen, H; Peng, W; Ma, Y; Hou, X; Guan, H; Liu, X; Xu, A
Year
2005
Is Peer Reviewed?
Yes
Journal
European Journal of Medicinal Chemistry
ISSN:
0223-5234
EISSN:
1768-3254
Volume
40
Issue
10
Page Numbers
991-1001
Language
English
PMID
15950325
DOI
10.1016/j.ejmech.2005.04.008
Web of Science Id
WOS:000232752500004
Abstract
To further our SAR study on the chemistry and antitumor activity/neurotoxicity of beta-carboline alkaloids, several series of beta-carboline derivatives with various substituents were designed and synthesized from the starting material l-tryptophan on the basis of harmine chemical structure. Cytotoxic activities of these compounds were investigated in vitro. The results showed that some beta-carboline derivatives had significant cytotoxic activities against human tumor cell lines. Among all the synthesized beta-carboline derivatives, the compounds 27, 28 and 32, having a benzyl substituent at both position-2 and 9, respectively, were found to be the most potent compounds with IC50 value lower than 50 microM against all human tumor cell lines examined. Acute toxicities and antitumor activities of the selected beta-carboline derivatives in mice were also evaluated. The results demonstrated that a benzyl substituent at position-2 increased the antitumor activity as well as acute toxicity significantly. However an (ethoxycarbonyl)amino substituent at position-3 reduced the acute toxicity as well as antitumor activity remarkedly. These data suggested that (1) the antitumor potencies of beta-carboline derivatives were enhanced by the introduction of benzyl substituent into the position-2; (2) the acute toxicity of beta-carboline derivatives reduced dramatically by the introduction of an appropriate substituent into the position-3 and 9; (3) the beta-carboline structure might be an important basis for the design and synthesis of new antitumor drugs with significant antitumor activity and low toxicity.
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