2. Academic Validation
  3. Synthesis and activity of benzimidazole N-Acylhydrazones against Trypanosoma cruzi, Leishmania amazonensis and Leishmania infantum

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

  • Bioorg Med Chem Lett. 2024 Jul 2:110:129876. doi: 10.1016/j.bmcl.2024.129876.
Laís G Ramos 1,  Kátia R de Souza 2,  Juliana M C Barbosa 3,  Kelly Salomão 3,  Policarpo A Sales Junior 4,  Valéria R A Pereira 4,  Silvane M F Murta 5,  Rafaela S Ferreira 6,  Talita C D Bernardes 6,  Solange M S V Wardell 7,  James L Wardell 8,  Nubia Boechat 9,  Samir A Carvalho 10
Affiliations

Affiliations

  • 1 Laboratorio de Sintese de Farmacos-LASFAR, Instituto de Tecnologia em Farmacos - Farmanguinhos - Fundação Oswaldo Cruz, 21041-250 Rio de Janeiro, RJ, Brazil; Laboratório de Físico-Química de Materiais, Seção de Engenharia Química, Instituto Militar de Engenharia, Praça General Tibúrcio 80, 22290-270 Rio de Janeiro, Brazil.
  • 2 Laboratório de Físico-Química de Materiais, Seção de Engenharia Química, Instituto Militar de Engenharia, Praça General Tibúrcio 80, 22290-270 Rio de Janeiro, Brazil.
  • 3 Laboratório de Biologia Celular, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, 21040-900 Rio de Janeiro, RJ, Brazil.
  • 4 Laboratório de Imunopatologia e Biologia Molecular, Departamento de Imunologia, Instituto Aggeu Magalhaes, Fundação Oswaldo Cruz, 50670-420 Recife, PE, Brazil.
  • 5 Grupo Genômica Funcional de Parasitos, Instituto René Rachou, Fiocruz Minas, 30190-002 Belo Horizonte, MG, Brazil.
  • 6 Laboratório de modelagem molecular e planejamento de fármacos, Departamento de Bioquímica e Imunologia, Universidade Federal de Minas Gerais, Avenida Antônio Carlos, 6627, Belo Horizonte, MG 31270-901, Brazil.
  • 7 CHEMSOL, 1 Harcourt Road, Aberdeen AB15 5NY, Scotland.
  • 8 Department of Chemistry, University of Aberdeen, Old Aberdeen AB24 3UE, Scotland.
  • 9 Laboratorio de Sintese de Farmacos-LASFAR, Instituto de Tecnologia em Farmacos - Farmanguinhos - Fundação Oswaldo Cruz, 21041-250 Rio de Janeiro, RJ, Brazil.
  • 10 Laboratorio de Sintese de Farmacos-LASFAR, Instituto de Tecnologia em Farmacos - Farmanguinhos - Fundação Oswaldo Cruz, 21041-250 Rio de Janeiro, RJ, Brazil. Electronic address: samircar@gmail.com.
PMID: 38964519 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.

Keywords

Antiprotozoal agents; Benzimidazole; Drug-discovery; Leishmania amazonensis; Leishmania infantum; N-Acylhydrazone; Trypanosoma cruzi.

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