In this paper, we report the design, synthesis and biological investigation of a series of peptidyl vinyl ketones obtained by modifying the P2 fragment of previously reported highly potent inhibitors of rhodesain, the main cysteine protease of Trypanosoma brucei rhodesiense. Investigation of the structure–activity relationship led us to identify new rhodesain inhibitors endowed with an improved selectivity profile (a selectivity index of up to 22000 towards the target enzyme), and/or an improved antitrypanosomal activity in the sub-micromolar range.

Peptidyl Vinyl Ketone Irreversible Inhibitors of Rhodesain: Modifications of the P2 Fragment

Santina Maiorana
Primo
;
Roberta Ettari
Secondo
;
Santo Previti;Maria Zappalà
Ultimo
2020-01-01

Abstract

In this paper, we report the design, synthesis and biological investigation of a series of peptidyl vinyl ketones obtained by modifying the P2 fragment of previously reported highly potent inhibitors of rhodesain, the main cysteine protease of Trypanosoma brucei rhodesiense. Investigation of the structure–activity relationship led us to identify new rhodesain inhibitors endowed with an improved selectivity profile (a selectivity index of up to 22000 towards the target enzyme), and/or an improved antitrypanosomal activity in the sub-micromolar range.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11570/3174563
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