Synthesis and in-vitro anti-leishmanial activity of (4-arylpiperazin-1-yl)(1-(thiophen-2-yl)-9H-pyrido[3,4-b]indol-3-yl)methanone derivatives

Abstract

In the present study, we have reported synthesis and biological evaluation of a series of fifteen 1-(thiophen-2-yl)-9H-pyrido[3,4-b]indole derivatives against both promastigotes and amastigotes of Leishmania parasites responsible for visceral (L. donovani) and cutaneous (L. amazonensis) leishmaniasis. Among these reported analogues, compounds 7b, 7c, 7f, 7g, 7i, 7j, 7m, 7o displayed potent activity (15.55, 7.70, 7.00, 3.80, 14.10, 9.25, 3.10, 4.85μM, respectively) against L. donovani promastigotes than standard drugs miltefosine (15.70μM) and pentamidine (32.70μM) with good selectivity index. In further, in-vitro evaluation against amastigote forms, two compounds 7g (8.80μM) and 7i (7.50μM) showed significant inhibition of L. donovani amastigotes. Standard drug amphotericin B is also used as control to compare inhibition potency of compounds against both promastigote (0.24μM) and amastigote (0.05μM) forms.

Keywords: Amastigote; Leishmaniasis; Promastigote; β-carboline.