title: Synthesis and in vitro cytotoxic evaluation of 1,3-bisubstituted and 1,3,9-trisubstituted beta-carboline derivatives.
abstract: A series of novel 1,3-bisubstituted and 1,3,9-trisubstituted beta-carboline derivatives was synthesized from the starting material l-tryptophan. Cytotoxic activities of these compounds were investigated in vitro. The results showed that 1,3,9-trisubstituted beta-carboline derivatives had higher cytotoxic activities in vitro than the corresponding 1,3-bisubstituted compounds. Among all the synthesized 1,3,9-trisubstituted beta-carboline derivatives, the compounds with a methyl substituent at position-1 displayed more potent cytotoxic activities, furthermore compound 5e having an ethoxycarbonyl substituent at position-3 and a pentafluorobenzyl at position-9, respectively, was found to be the most potent compounds of this series with IC(50) value of 4 uM against BGC-823 cell lines. These data suggested that (1) the cytotoxic potencies of beta-carboline derivatives were enhanced by the introduction of appropriate substituents into position-1 and position-9 in beta-carboline; (2) the beta-carboline structure might be an important basis for the design and synthesis of new antitumor drugs; (3) the methyl substituent at position-1, the pentafluorobenzyl group at position-9 and the ethoxycarbonyl substituent at position-3 were the optimal combination for the improvement of cytotoxic activity of the beta-carboline derivatives.
authors.affiliation: Department of Biochemistry and Center for Biopharmaceutical Research, College of Life Sciences, Sun Yat-sen (Zhongshan) University, 135 Xin Gang Xi Road, Guangzhou 510275, China.
authors.forename: Rihui
authors.initials: R
authors.lastname: Cao
authors.forename: Wenlie
authors.initials: W
authors.lastname: Peng
authors.forename: Hongsheng
authors.initials: H
authors.lastname: Chen
authors.forename: Xuerui
authors.initials: X
authors.lastname: Hou
authors.forename: Huaji
authors.initials: H
authors.lastname: Guan
authors.forename: Qi
authors.initials: Q
authors.lastname: Chen
authors.forename: Yan
authors.initials: Y
authors.lastname: Ma
authors.forename: Anlong
authors.initials: A
authors.lastname: Xu
mesh_terms: D002243:Carbolines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D049109:Cell Proliferation / Q000187:drug effects*; D006801:Humans; D066298:In Vitro Techniques; D020128:Inhibitory Concentration 50; D009369:Neoplasms / Q000188:drug therapy*; D014407:Tumor Cells, Cultured
chemical_list: D002243:Carbolines