Highly tunable thiosulfonates as a novel class of cysteine protease inhibitors with anti-parasitic activity against Schistosoma mansoni

Ward, D.J., Van de Langemheen, H., Koehne, E., Kreidenweiss, A. and Liskamp, R.M.J. (2019) Highly tunable thiosulfonates as a novel class of cysteine protease inhibitors with anti-parasitic activity against Schistosoma mansoni. Bioorganic and Medicinal Chemistry, 27(13), pp. 2857-2870. (doi: 10.1016/j.bmc.2019.05.014) (PMID:31126821)

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.

• Item Type: Articles
• Additional Information: This research was supported by the University of Glasgow.
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Liskamp, Professor Robert and Ward, Mr David and Van De Langemheen, Mr Helmus
• Authors: Ward, D.J., Van de Langemheen, H., Koehne, E., Kreidenweiss, A., and Liskamp, R.M.J.
• College/School: College of Science and Engineering > School of Chemistry
• Journal Name: Bioorganic and Medicinal Chemistry
• Publisher: Elsevier
• ISSN: 0968-0896
• ISSN (Online): 1464-3391
• Published Online: 13 May 2019
• Copyright Holders: Copyright © 2019 Elsevier Ltd.
• First Published: First published in Bioorganic and Medicinal Chemistry 27(13): 2857-2870
• Publisher Policy: Reproduced in accordance with the publisher copyright policy