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

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.PMID:38677111 | DOI:10.1016/j.bmc.2024.117736

Source: Bioorganic and Medicinal Chemistry - April 27, 2024 Category: Chemistry Authors: Guilherme Freitas de Lima Hercos Mariza Gabriela Faleiro de Moura Lodi Cruz Ana Clara Cassiano Martinho Daniela de Melo Resende Danilo Farago Nascimento Paula Derksen Macruz Eduardo Jorge Pilau Silvane Maria Fonseca Murta Celso de Oliveira Rezende J únio Source Type: research