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

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• 作者：Letí ; cia de Almeida^a ; ^{leticia.almeida.le@gmail.com" class="auth_mail" title="E-mail the corresponding author} ; Karina Ferreira Alves^a ; Claudia Mara Maciel-Rezende^b ; Larissa de Oliveira Passos Jesus^c ; Francieli Ribeiro Pires^b ; Claudio Viegas Junior^b ; Mario Augusto Izidoro^d ; Wagner Alves de Souza Jú ; dice^c ; Marcelo Henrique dos Santos^b ; Marcos José ; Marques^a
• 关键词：Z-F-R-MCA ; carbobenzoxicarbonil-Phe-Arg-7-amido-4-methylcoumarin ; CPs ; cysteine proteases ; MTT ; 3-(4 ; 5-dimethylthiazol-2-yl)-2 ; 5-diphenyltetrazolium bromide ; FBS ; fetal bovine serum ; 1a ; 2-hydroxy-4-methoxybenzophenone ; 1b ; 2-hydroxy-4- O -butylbenzophenone ; 1c ; 2-hydroxy-4- O -(3 ; 3-dimethyl)-allylbenzophenone ; 2a ; 4-methoxybenzophenone ; 2b ; 4-butoxybenzophenone ; 2c ; 4- O -(3 ; 3-dimethyl)-allylbenzophenone ; 3a ; 4 ; 4&prime ; -di-methoxybenzophenone ; AmpB ; Amphotericin B ; DMSO ; dimethylsulfoxide ; IC50
• 刊名：Biomedicine & Pharmacotherapy
• 出版年：2015
• 出版时间：October 2015
• 年：2015
• 卷：75
• 期：Complete
• 页码：93-99
• 全文大小：1199 K

文摘

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.