UMR CNRS 6264, Laboratoire Chimie Provence, Aix-Marseille Université-Laboratoire de Pharmacochimie Radicalaire, Faculté de Pharmacie, 27 Boulevard Jean-Moulin, 13385 Marseille Cedex 05, France.
Biomed Pharmacother. 2012 Jul;66(5):339-47. doi: 10.1016/j.biopha.2011.12.006. Epub 2012 Feb 17.
The synthesis of β-carbolines and their in vitro antiplasmodial and antileishmanial activities were described herein. These molecules have also been studied concerning their in vitro cytotoxicity toward the human cell line THP1, in order to calculate their respective selectivity indexes (SI). Among the 20 tested molecules, four exhibited significant antiplasmodial activity on the W2 multi-resistant Plasmodium falciparum strain (0.7 < IC₅₀ < 1.7 μM), in comparison with two references drugs (chloroquine and doxycycline), and a low cytotoxicity. These β-carbolines were also evaluated concerning their in vitro antileshmanial activity on Leishmania donovani promastigotes, permitting to identify an antileshmanial hit compound, displaying quite promising activity (IC₅₀ = 6.1 μM) in comparison with amphotericin B and pentamidine chosen as reference drugs. Finally, structure-activity relationships were discussed, pointing out that molecules presenting a para-substituted phenyl moiety at position 1 of the β-carboline ring displayed the best biological profile.
本文描述了β-咔啉的合成及其体外抗疟原虫和抗利什曼原虫活性。还研究了这些分子对人 THP1 细胞系的体外细胞毒性，以计算它们各自的选择性指数（SI）。在测试的 20 种分子中，有 4 种对 W2 多耐药性恶性疟原虫菌株（0.7<IC₅₀<1.7μM）表现出显著的抗疟原虫活性，与两种参考药物（氯喹和强力霉素）相比，细胞毒性较低。还评估了这些β-咔啉对利什曼原虫前鞭毛体的体外抗利什曼原虫活性，鉴定出一种抗利什曼原虫的有效化合物，与作为参考药物的两性霉素 B 和戊烷脒相比，具有相当有前景的活性（IC₅₀=6.1μM）。最后，讨论了构效关系，指出在β-咔啉环的 1 位带有对位取代苯基部分的分子表现出最佳的生物学特征。
