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

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

  • Bioorg Med Chem. 2024 May 1:105:117736. doi: 10.1016/j.bmc.2024.117736.
Guilherme Freitas de Lima Hercos 1,  Mariza Gabriela Faleiro de Moura Lodi Cruz 2,  Ana Clara Cassiano Martinho 1,  Daniela de Melo Resende 2,  Danilo Farago Nascimento 1,  Paula Derksen Macruz 3,  Eduardo Jorge Pilau 3,  Silvane Maria Fonseca Murta 2,  Celso de Oliveira Rezende Júnior 4
Affiliations

Affiliations

  • 1 Laboratório de Síntese de Candidatos a Fármacos (LaSFar), Instituto de Química, Universidade Federal de Uberlândia (UFU), Uberlândia, MG 38400-902, Brazil.
  • 2 Grupo de Genômica Funcional de Parasitos, Instituto René Rachou, Fundação Oswaldo Cruz (FIOCRUZ Minas), Belo Horizonte, MG 30190-002, Brazil.
  • 3 Laboratório de Biomoléculas e Espectrometria de Massas (LaBioMass), Universidade Estadual de Maringá (UEM), Maringá, PR 807020-900, Brazil.
  • 4 Laboratório de Síntese de Candidatos a Fármacos (LaSFar), Instituto de Química, Universidade Federal de Uberlândia (UFU), Uberlândia, MG 38400-902, Brazil. Electronic address: [email protected].
PMID: 38677111 DOI: 10.1016/j.bmc.2024.117736
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.

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