A chemoselective one-pot synthesis of pharmaceutically prospective indole-pyrrole hybrids by the formal [3 + 2] cycloaddition of 3-cyanoacetyl indoles (CAIs) with 1,2-diaza-1,3-dienes (DDs) has been developed. The new indole-pyrrole hybrids were phenotypically screened for efficacy against Leishmania infantum promastigotes. The most active compounds 3c, 3d, and 3j showed IC50 < 20 μM and moderate cytotoxicity, lower than miltefosine. Compound 3d was the most active with IC50 = 9.6 μM and a selectivity index of 5. Consequently, 3d could be a new lead compound for the generation of a new class of antileishmanial hybrids.
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