CLOFAZIMINE ANALOGS WITH ANTILEISHMANIAL AND ANTIMALARIAL ACTIVITIES

Clofazimine is a fat-soluble riminophenazine dye used in combination with rifampicin and dapsone as multidrug therapy (MDT) for the treatment of leprosy. This agent is known to have antileishmanial effects both in vitro and in vivo.[1] Tetramethylpiperidine –substituted phenazines, structurally related to clofazimine, have been described to be endowed with activity against multidrug resistant strains of Plasmodium falciparum.[2] In the search for more effective alternatives to the presently used antileishmanial drugs and with the aim to study more thorougly the antimalarial potentialities of this kind of structures, we synthesized a set of novel iminophenazines bearing a bicyclic basic head linked through an alkylic chain to the imino nitrogen in position 3 on the phenazine nucleus. The new compounds inhibited the growth of different strains of Leishmania promastigotes as well as chloroquine sensitive (CQ-S) and chloroquine resistant (CQ-R) strains of P. falciparum with IC50 in submicromolar range whereas clofazimine was 10-20 –fold less active.