Indolylquinoline derivatives are cytotoxic to Leishmania donovani promastigotes and amastigotes in vitro and are effective in treating murine visceral leishmaniasis

A wide variety of biologically active compounds contain indole and quinolin e nuclei. Some novel indolylquinoline derivatives were synthesized from ind ole by Friedel-Crafts acylation reaction. Out of the four derivatives teste d, 2-(2"-acetamidobenzyl)-3-(3'-indolylquinoline) (C) had no effect on the promastigotes or amastigotes of Leishmania donovani in vitro. The remaining three analogues, 2-(2"-dichloroacetamidobenzyl)-3-(3'-indolylquinoline) (A ), 2-(2"-chloroacetamidobenzyl)-3-(3'-indolylquinoline) (B), and 2-(2"-amin obenzyl)-3-(3'-indolylquinoline) (D), inhibited the growth of L. donovani p romastigotes in vitro and were cytotoxic to both the promastigote and amast igote forms of the parasite. These three derivatives were also effective in eliminating L. donovani amastigotes from BALB/c mouse peritoneal macrophag es in vitro. One indolylquinoline derivative [A] was used to treat establis hed visceral leishmaniasis in BALB/c mice. This compound was significantly more effective than sodium antimony gluconate (SAG) in reducing the splenic parasite load at a much lower concentration (5% of SAG). Our results sugge st that indolylquinoline derivatives may be exploited as antileishmanial ag ents.