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Leishmaniasis are group of neglected diseases with worldwide distribution that affect about 12 million people. The current treatment is limited and may cause severe adverse effects, and thus, the search for new drugs more effective and less toxic is relevant. We have previously investigated the immunomodulatory effects of LASSBio-1386, an  N -acylhydrazone derivative. Here we investigated the  in vitro  and  in vivo  activity of LASSBio-1386 against  L. amazonensis . LASSBio-1386 inhibited the proliferation of promastigotes of  L. amazonensis  (EC 50  = 2.4 ± 0.48 µM), while presenting low cytotoxicity to macrophages (CC 50  = 74.1 ± 2.9 µM).  In vitro  incubation with LASSBio-1386 reduced the percentage of  Leishmania -infected macrophages and the number of intracellular parasites (EC 50  = 9.42 ± 0.64 µM). Also,  in vivo  treatment of BALB/c mice infected with  L. amazonensis  resulted in a decrease of lesion size, parasitic load and caused histopathological alterations, when compared to vehicle-treated control. Moreover, LASSBio-1386 caused ultrastructural changes, arrested cell cycle in G0/G1 phase and did not alter the membrane mitochondrial potential of  L. amazonensis . Aiming to its possible molecular interactions, we performed docking and molecular dynamics studies on  Leishmania  phosphodiesterase B1 (PDB code: 2R8Q) and LASSBio-1386. The computational analyses suggest that LASSBio-1386 acts against  Leishmania  through the modulation of leishmanial PDE activity. In conclusion, our results indicate that LASSBio-1386 is a promising candidate for the development of new leishmaniasis treatment.

frontiers in pharmacology

In Vitro, In Vivo and In Silico Effectiveness of LASSBio-1386, an N-Acyl Hydrazone Derivative Phosphodiesterase-4 Inhibitor, Against Leishmania amazonensis