Balfour MN, Alcantara LM, Ferreira TCS, Menezes CMS, Moraes CB, Freitas-Junior LHand Stefani HA
Leishmaniasis is a devastating parasitic disease of medical and veterinary importance that is endemic across the tropics. It can be either disfiguring or lethal in its most severe forms and it lacks appropriate treatment. Several species of the protozoan parasite Leishmania can cause Leishmaniasis in human, which further complicates the development of new therapeutics because the different species are genotypically and phenotypically diverse. We have previously reported the anti-protozoal activity of 4-substituted 2-(1H-pyrrolo [3, 2-c] pyridin-2-yl) propan-2-ols against the related protozoan, Trypanosoma cruzi. Herein we report the biological activity of some of these compounds against intracellular amastigotes of three of the most clinically relevant Leishmania species: L. amazonensis, L. braziliensis and L. infantum. Four of the tested compound showed activity against the three Leishmania species, albeit with varied potency. The compounds were also cytotoxic to the human host cells at higher concentrations. A molecular modeling study suggested that these compounds are capable of binding to the ADP site and thus inhibit the leishmanial nucleoside diphosphate kinase (NDK). These results show that 4-substituted 2-(1H-pyrrolo [3, 2-c] pyridin-2-yl) propan-2-ols may potentially become chemical entities with broad-spectrum anti-leishmanial activity.