Synthesis and activity of benzimidazole N-Acylhydrazones against Trypanosoma cruzi, Leishmania amazonensis and Leishmania infantum

[Display omitted] •Planning of new Benzimidazole N-acylhydrazones with antitrypanosomal activity.•Biological evaluation of the compounds against T. cruzi strains (Y and Tulahuen)•Biological evaluation of the compounds against L. amazonensis and L. infantum. In this study, we present the design, synt...

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Published in:	Bioorganic & medicinal chemistry letters Vol. 110; p. 129876
Main Authors:	Ramos, Laís G., de Souza, Kátia R., Barbosa, Juliana M.C., Salomão, Kelly, Sales Junior, Policarpo A., Pereira, Valéria R.A., Murta, Silvane M.F., Ferreira, Rafaela S., Bernardes, Talita C.D., Wardell, Solange M.S.V., Wardell, James L., Boechat, Nubia, Carvalho, Samir A.
Format:	Journal Article
Language:	English
Published:	England Elsevier Ltd 15-09-2024
Subjects:	Animals Antiprotozoal agents Antiprotozoal Agents - chemical synthesis Antiprotozoal Agents - chemistry Antiprotozoal Agents - pharmacology Benzimidazole Benzimidazoles - chemical synthesis Benzimidazoles - chemistry Benzimidazoles - pharmacology Dose-Response Relationship, Drug Drug-discovery Hydrazones - chemical synthesis Hydrazones - chemistry Hydrazones - pharmacology Leishmania - drug effects Leishmania amazonensis Leishmania infantum Leishmania infantum - drug effects Molecular Structure N-Acylhydrazone Parasitic Sensitivity Tests Structure-Activity Relationship Trypanocidal Agents - chemical synthesis Trypanocidal Agents - chemistry Trypanocidal Agents - pharmacology Trypanosoma cruzi Trypanosoma cruzi - drug effects Leishmania infantum Drug-discovery Benzimidazole Antiprotozoal agents Leishmania amazonensis N-Acylhydrazone Trypanosoma cruzi
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Summary:	[Display omitted] •Planning of new Benzimidazole N-acylhydrazones with antitrypanosomal activity.•Biological evaluation of the compounds against T. cruzi strains (Y and Tulahuen)•Biological evaluation of the compounds against L. amazonensis and L. infantum. 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.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	0960-894X 1464-3405 1464-3405
DOI:	10.1016/j.bmcl.2024.129876