| Author | Hercos, Guilherme Freitas de Lima | |
| Author | Cruz, Mariza Gabriela Faleiro de Moura Lodi | |
| Author | Martinho, Ana Clara Cassiano | |
| Author | Resende, Daniela de Melo | |
| Author | Nascimento, Danilo Farago | |
| Author | Macruz, Paula Derksen | |
| Author | Pilau, Eduardo Jorge | |
| Author | Murta, Silvane Maria Fonseca | |
| Author | Rezende Júnior, Celso de Oliveira | |
| Access date | 2024-06-24T12:33:41Z | |
| Available date | 2024-06-24T12:33:41Z | |
| Document date | 2024 | |
| 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. | en_US |
| ISSN | 0968-0896 | en_US |
| URI | https://www.arca.fiocruz.br/handle/icict/64612 | |
| Language | eng | en_US |
| Publisher | Elsevier | en_US |
| Rights | restricted access | |
| Title | Optimization of benzenesulfonyl derivatives as anti-Trypanosomatidae agents: Structural design, synthesis, and pharmacological assessment against Trypanosoma cruzi and Leishmania infantum. | en_US |
| Type | Article | |
| 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. | en_US |
| Affilliation | Universidade Federal de Uberlândia. Instituto de Química. Laboratório de Síntese de Candidatos a Fármacos. Uberlândia, MG, Brazil | en_US |
| Affilliation | Fundação Oswaldo Cruz. Instituto René Rachou. Grupo de Genômica Funcional de Parasitos. Belo Horizonte, MG, Brazil | en_US |
| Affilliation | Universidade Federal de Uberlândia. Instituto de Química. Laboratório de Síntese de Candidatos a Fármacos. Uberlândia, MG, Brazil | en_US |
| Affilliation | Fundação Oswaldo Cruz. Instituto René Rachou. Grupo de Genômica Funcional de Parasitos. Belo Horizonte, MG, Brazil | en_US |
| Affilliation | Universidade Federal de Uberlândia. Instituto de Química. Laboratório de Síntese de Candidatos a Fármacos. Uberlândia, MG, Brazil | en_US |
| Affilliation | Universidade Estadual de Maringá. Laboratório de Biomoléculas e Espectrometria de Massas. Maringá, PR, Brazil | en_US |
| Affilliation | Universidade Estadual de Maringá. Laboratório de Biomoléculas e Espectrometria de Massas. Maringá, PR, Brazil | en_US |
| Affilliation | Fundação Oswaldo Cruz. Instituto René Rachou. Grupo de Genômica Funcional de Parasitos. Belo Horizonte, MG, Brazil | en_US |
| Affilliation | Universidade Federal de Uberlândia. Instituto de Química. Laboratório de Síntese de Candidatos a Fármacos. Uberlândia, MG, Brazil | en_US |
| Subject | Chagas disease | en_US |
| Subject | Hit-to-lead optimization | en_US |
| Subject | Lead candidates | en_US |
| Subject | Leishmaniasis | en_US |
| Subject | Neglected tropical diseases | en_US |
| Subject | Structure-activity relationship | en_US |
| Embargo date | 2100-12-31 | |
