In vitro cytotoxic activity of isolated acridones alkaloids from Zanthoxylum leprieurii Guill. et Perr

• Published in: Bioorganic & medicinal chemistry 2010-05, Vol.18 (10), p.3601-3605
• Main Authors: Ngoumfo, Rostand M., Jouda, Jean-Bosco, Mouafo, Ferdinand T., Komguem, Justin, Mbazoa, Céline D., Shiao, Tze Chieh, Choudhary, Mohammed I., Laatsch, Hartmut, Legault, Jean, Pichette, André, Roy, René
• Format: Article
• Language: English
• Subjects: Acridones; Acridones - pharmacology; Alkaloids - pharmacology; Animals; Antineoplastic Agents, Phytogenic - pharmacology; Artemia - drug effects; Colorectal adenocarcinoma; Cytotoxity; Female; Humans; Inhibitory Concentration 50; Lung carcinoma; Phytotherapy - methods; Plant Extracts - chemistry; Plant Extracts - pharmacology; Plant Roots - chemistry; Tumor Cells, Cultured; Zanthoxylum - chemistry
• ISSN: 0968-0896; 1464-3391
• DOI: 10.1016/j.bmc.2010.03.040

A family of acridones was isolated from Zanthoxylum leprieurii and their cytotoxicity was evaluated against lung carcinoma cells (A549), colorectal adenocarcinoma cells (DLD-1) and normal cells (WS1). In contrast to positive control etoposide, the cytotoxicity of the most active compound 4 was found to be selective against cancer cells in comparison to normal cells. Chemical investigation of the roots and fruits of Zanthoxylum leprieurii Guill. et Perr. led to the isolation of three new alkaloids including two acridone derivatives, 3-hydroxy-1,4-dimethoxy-10-methyl-9-acridone ( 2) and 3-hydroxy-1,2-dimethoxy-10-methyl-9-acridone ( 3) named helebelicine A and B, respectively, and one secobenzo[ c]phenantridine, 10- O-demethyl-12- O-methylarnottianamide ( 10), together with thirteen other compounds. The structures of compounds 2, 3 and 10 as well as those of the known compounds were elucidated by using spectroscopic methods and by comparison with reported data. The brine-shrimp ( artemia salina) lethality bioassay of the chloroform extract of the fruits showed modest cytotoxicity with LD 50 at 13.1 μg/mL. Isolated compounds 1, 4– 6 were found to be moderately active against lung carcinoma cells (A549), colorectal adenocarcinoma cells (DLD-1) and normal cells (WS1) with IC 50 values ranging from 27 to 77 μM. In contrast to the positive control etoposide used, the cytotoxicity of the most active compound 4 was found to be selective against cancer cells in comparison to normal cells WS1 with IC 50 of 51 ± 8 μM and 4.3 ± 0.4 μM, respectively.