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Benzophenone derivatives as cysteine protease inhibitors and biological activity against Leishmania(L.) amazonensis amastigotes

2015; Elsevier BV; Volume: 75; Linguagem: Inglês

10.1016/j.biopha.2015.08.030

1950-6007

Letícia de Almeida, Karina Ferreira Alves, Claudia Mara Maciel-Rezende, Larissa de Oliveira Passos Jesus, Francieli Ribeiro Pires, Cláudio Viegas, Mario Augusto Izidoro, Wagner Alves de Souza Júdice, Marcelo Henrique dos Santos, Marcos José Marques,

Trypanosoma species research and implications

The leishmanicidal potential of benzophenones has been described, some of them highlighting their potential as cysteine protease inhibitors. Therefore, this work described leishmanicidal activity of nine benzophenone derivatives (1a–c;2a–c;3a–c) against intramacrophage amastigote forms of Leishmania(L.) amazonensis (IC50) and the cytotoxic effect on murine peritoneal macrophages (CC50). The derivative 1c exhibited a selectivity index SI (CC50/IC50) of 6.7, besides cytotoxicity lower than Amphotericin B (p < 0.05). Moreover it showed inhibitory activity against papain (42.8 ± 0.3, p < 0.05), and when tested on trypanosomatids cysteine proteases 1c also proved to be a potent inhibitor of rCPB2.8, rCPB3.0 and cruzain, showing non-competitive inhibition mechanism by enzymatic assays in vitro.So, benzophenone 1c is interesting drug candidate prototype, with a multi-target directed mode of action, inhibiting rCPB2.8, rCPB3.0 and cruzain.