title: Synthesis and in vitro cytotoxic evaluation of novel 3,4,5-trimethoxyphenyl substituted beta-carboline derivatives.
abstract: To elucidate further our SARs' study on the chemistry and cytotoxic activity and probe the structural requirement for the potent antitumor activity of beta-carbolines, a series of novel 1,9-disubstituted and 1,3,9-trisubstituted beta-carboline derivatives were designed and synthesized from the starting material L-tryptophan and 3,4,5-trimethoxybenezaldehyde. Cytotoxic activities of these compounds in vitro were investigated, and the SARs associated with position-1, 3 and 9 substituents in beta-carbolines have also been discussed. It has been observed that these compounds only displayed moderate to weak cytotoxic activities. Interestingly, most of the investigated compounds displayed selectively cytotoxic activities to human BCG-823 cell lines with IC(50) value lower than 100 microM. In addition, the short alkyl substituents in position-9 increased the cytotoxic activities with the tendency of n-butyl > ethyl > methyl. These data confirmed that (1) an alkyl substituent at position-9 of beta-carboline nucleus plays an important role in determining their antitumor activities; (2) different beta-carbolines bearing various substituents in beta-carboline nucleus interacted selectively with specific targets leading to the difference of biochemical and pharmacological effects.
authors.affiliation: School of Life Sciences, Sun Yat-sen (Zhongshan) University, 135 Xin Gang Xi Road, Guangzhou 510275, PR China.
authors.forename: Qifeng
authors.initials: Q
authors.lastname: Wu
authors.forename: Rihui
authors.initials: R
authors.lastname: Cao
authors.forename: Manxiu
authors.initials: M
authors.lastname: Feng
authors.forename: Xiangdong
authors.initials: X
authors.lastname: Guan
authors.forename: Chunming
authors.initials: C
authors.lastname: Ma
authors.forename: Jinbing
authors.initials: J
authors.lastname: Liu
authors.forename: Huacan
authors.initials: H
authors.lastname: Song
authors.forename: Wenlie
authors.initials: W
authors.lastname: Peng
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D001547:Benzaldehydes; D002243:Carbolines / Q000138:chemical synthesis* / Q000494:pharmacology; D045744:Cell Line, Tumor; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D020128:Inhibitory Concentration 50; D013329:Structure-Activity Relationship; D014364:Tryptophan
chemical_list: D000970:Antineoplastic Agents; D001547:Benzaldehydes; D002243:Carbolines; D014364:Tryptophan; C032175:benzaldehyde