{Reference Type}: Journal Article
{Title}: Synthesis and activity of benzimidazole N-Acylhydrazones against Trypanosoma cruzi, Leishmania amazonensis and Leishmania infantum.
{Author}: Ramos LG;de Souza KR;Barbosa JMC;Salomão K;Sales Junior PA;Pereira VRA;Murta SMF;Ferreira RS;Bernardes TCD;Wardell SMSV;Wardell JL;Boechat N;Carvalho SA;
{Journal}: Bioorg Med Chem Lett
{Volume}: 110
{Issue}: 0
{Year}: 2024 Jul 2
{Factor}: 2.94
{DOI}: 10.1016/j.bmcl.2024.129876
{Abstract}: In this study, we present the design, synthesis, and cytotoxic evaluation of a series of benzimidazole N-acylhydrazones against strains of T. cruzi (Y and Tulahuen) and Leishmania species (L. amazonensis and L. infantum). Compound (E)-N'-((5-Nitrofuran-2-yl)methylene)-1H-benzo[d]imidazole-2-carbohydrazide demonstrated significant activity against both trypomastigote and amastigote forms (Tulahuen strain), with an IC50/120 h of 0.033 μM and a selectivity index (SI) of 7680. This represents a potency 46 times greater than that of benznidazole (IC50/120 h = 1.520 μM, SI = 1390). Another compound (E)-N'-(2-Hydroxybenzylidene)-1H-benzo[d]imidazole-2-carbohydrazide showed promising activity against both trypomastigote and amastigote forms (Tulahuen strain), with an IC50/120 h of 3.600 μM and an SI of 14.70. However, its efficacy against L. infantum and L. amazonensis was comparatively lower. These findings provide valuable insights for the development of more effective treatments against Trypanosoma cruzi.