Optimization of benzenesulfonyl derivatives as anti-Trypanosomatidae agents: Structural design, synthesis, and pharmacological assessment against Trypanosoma cruzi and Leishmania infantum.

Universidade Federal de Uberlândia. Instituto de Química. Laboratório de Síntese de Candidatos a Fármacos. Uberlândia, MG, Brazil
Fundação Oswaldo Cruz. Instituto René Rachou. Grupo de Genômica Funcional de Parasitos. Belo Horizonte, MG, Brazil
Universidade Federal de Uberlândia. Instituto de Química. Laboratório de Síntese de Candidatos a Fármacos. Uberlândia, MG, Brazil
Fundação Oswaldo Cruz. Instituto René Rachou. Grupo de Genômica Funcional de Parasitos. Belo Horizonte, MG, Brazil
Universidade Federal de Uberlândia. Instituto de Química. Laboratório de Síntese de Candidatos a Fármacos. Uberlândia, MG, Brazil
Universidade Estadual de Maringá. Laboratório de Biomoléculas e Espectrometria de Massas. Maringá, PR, Brazil
Universidade Estadual de Maringá. Laboratório de Biomoléculas e Espectrometria de Massas. Maringá, PR, Brazil
Fundação Oswaldo Cruz. Instituto René Rachou. Grupo de Genômica Funcional de Parasitos. Belo Horizonte, MG, Brazil
Universidade Federal de Uberlândia. Instituto de Química. Laboratório de Síntese de Candidatos a Fármacos. Uberlândia, MG, Brazil

Abstract

Leishmaniasis and Chagas disease are neglected tropical diseases caused by Trypanosomatidae parasites. Given the numerous limitations associated with current treatments, such as extended treatment duration, variable efficacy, and severe side effects, there is an urgent imperative to explore novel therapeutic options. This study details the early stages of hit-to-lead optimization for a benzenesulfonyl derivative, denoted as initial hit, against Trypanossoma cruzi (T. cruzi), Leishmania infantum (L. infantum) and Leishmania braziliensis (L. braziliensis). We investigated structure - activity relationships using a series of 26 newly designed derivatives, ultimately yielding potential lead candidates with potent low-micromolar and sub-micromolar activities against T. cruzi and Leishmania spp, respectively, and low in vitro cytotoxicity against mammalian cells. These discoveries emphasize the significant promise of this chemical class in the fight against Chagas disease and leishmaniasis.

Keywords

Chagas disease
Hit-to-lead optimization
Lead candidates
Leishmaniasis
Neglected tropical diseases
Structure-activity relationship

Publisher

Elsevier

Citation

DE LIMA HERCOS, Guilherme Freitas de et al. Optimization of benzenesulfonyl derivatives as anti-Trypanosomatidae agents: Structural design, synthesis, and pharmacological assessment against Trypanosoma cruzi and Leishmania infantum. Bioorganic & Medicinal Chemistry, v. 105, p. 117736, 2024. doi.org/10.1016/j.bmc.2024.117736.

ISSN

0968-0896

Please use this identifier to cite or link to this item: https://www.arca.fiocruz.br/handle/icict/64612

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Copyright

Restricted access

Embargo date

2100-12-31

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