Hit-to-lead optimization of novel phenyl imidazole carboxamides that are active against Leishmania donovani

Evaluation and discovery of novel benzothiazole derivatives as promising hits against Leishmania infantum

“…Their efficiency is limited, sometimes being case‐dependent, they cause heavy side effects, and/or are toxic for the human organism, in addition to their relatively high cost which prevents those who need it to accessing these treatments and to the apparition of drug‐resistant strains (Alves et al., 2018; Dorlo et al., 2012; Field et al., 2017; Freitas‐Junior et al., 2012; Sales et al., 2017; Sunyoto et al., 2019). Therefore, important research efforts from public organizations (DNDi, 2023b), pharmaceutical companies (Peña et al., 2015) and academic research groups (Cassiano Martinho et al., 2022; Ferreira et al., 2021; Jacques Dit Lapierre et al., 2023; Koovits, Dessoy, Matheeussen, Maes, Caljon, Ferreira, et al., 2020; Lal et al., 2023; McNamara et al., 2022) have been performed over the last decades, in order to identify clinical candidates which might overcome the shortcomings of the current treatments (Chatelain, 2015; Field et al., 2017; Koovits, Dessoy, Matheeussen, Maes, Caljon, Mowbray, et al., 2020). Among the resulting literature from such works, benzothiazole‐containing compounds can be encountered in numerous studies targeting diverse parasites, in which the inclusion of a benzothiazole fragment provides compounds active against Trypanosoma brucei (Berg et al., 2001; Brown et al., 2020; de Oliveira Viana et al., 2019; Linciano et al., 2019), T. cruzi (Berg et al., 2001; Cuevas‐Hernández et al., 2020; Fleau et al., 2019; Martínez‐Cerón et al., 2021), L. infantum (de Oliveira Viana et al., 2019), Plasmodium falciparum (Berg et al., 2001), and Cryptosporidium parvum (Oboh et al., 2023), among others.…”