Synthesis and in vitro cytotoxic evaluation of 1,3-bisubstituted and 1,3,9-trisubstituted beta-carboline derivatives
| Autor: | Qi Chen, Rihui Cao, Anlong Xu, Huaji Guan, Xuerui Hou, Wenlie Peng, Hongsheng Chen, Yan Ma |
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| Rok vydání: | 2004 |
| Předmět: |
Pharmacology
β carboline derivatives Chemistry Stereochemistry Organic Chemistry Substituent General Medicine In Vitro Techniques Chemical synthesis In vitro chemistry.chemical_compound Inhibitory Concentration 50 Cell culture Neoplasms Drug Discovery Tumor Cells Cultured Cytotoxic T cell Optimal combination Humans Cytotoxicity Carbolines Cell Proliferation |
| Zdroj: | European journal of medicinal chemistry. 40(3) |
| ISSN: | 0223-5234 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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