Preparation and antiprotozoal evaluation of promising β-carboline alkaloids

The synthesis of beta-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 mu M), in comparison with two references drugs (chloroquine and doxycycline), and a low cytotoxicity. These beta-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 mu M) 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 beta-carboline ring displayed the best biological profile. (C) 2012 Elsevier Masson SAS. All rights reserved.