Highly tunable thiosulfonates as a novel class of cysteine protease inhibitors with anti-parasitic activity against Schistosoma mansoni |
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Authors: | DJ Ward H Van de Langemheen E Koehne A Kreidenweiss RMJ Liskamp |
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Institution: | 1. School of Chemistry, Joseph Black Building, University of Glasgow, University Avenue, Glasgow G12 8QQ, UK;2. Institute of Tropical Medicine, University of Tübingen, Wilhelmstrasse 27, D-72074 Tübingen, Germany |
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Abstract: | The development of a new class of cysteine protease inhibitors utilising the thiosulfonate moiety as an SH specific electrophile is described. This moiety has been introduced into suitable amino acid derived building blocks, which were incorporated into peptidic sequences leading to very potent i.e. sub micromolar inhibitors of the cysteine protease papain in the same range as the vinyl sulfone based inhibitor K11777. Therefore, their inhibitory effect on Schistosoma mansoni, a human blood parasite, that expresses several cysteine proteases, was evaluated. The homophenylalanine side chain containing compounds 27–30 and especially 36 showed promising activities compared with K11777 and warrant further investigations of these peptidic thiosulfonate inhibitors as new potential anti-parasitic compounds. |
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Keywords: | Corresponding authors Thiosulfonate Cysteine protease inhibitor Schistosomiasis Tunable electrophilic trap Docking study |
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