Synthesis and Antitumor Activities ofβ-Carboline Derivatives

Chinese Journal of Organic Chemistry
2013.0

Abstract

In search of more effective antitumor agents, based on the previous results of computer aided drug design. The starting material L-tryptophan reacted with formaldehyde via Pictet-Spengler condensation and followed by oxidation and decarboxylation to afford the intermediate beta-carboline. The intermediate was further reacted with halogenated hydrocarbon by N-9-alkylation and N-2-quaternarization to obtain new beta-carboline derivatives. Fourteen novel beta-carboline derivatives were synthesized and characterized by H-1 NMR, IR, MS and elemental analysis. Compound 5h was further studied by X-ray single crystal diffraction analysis. The antitumor activity of the target compounds was studied by MTT method. The results demonstrated that N-2-quaternarized compounds (5a similar to 5n) had more remarkable cytotoxic activities in vitro than 9-phenylpropyl-beta-carboline (4). The tumor inhibition rates of the selected compounds 5e and 5h in mice bearing Lewis lung cancer. The compound 9 showed inhibition activity on transplanting-tumor growth of Lewis lung cancer.

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