ArticleCommunications chemistry2024
Discovery of Trypanosoma brucei inhibitors enabled by a unified synthesis of diverse sulfonyl fluorides.
Article in Communications chemistry, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.
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Who cites it
4 citing papers in PubMed.
- A Synergistic Inhibitor Development Strategy Against Human UDP-Galactose-4-Epimerase.Angewandte Chemie (International ed. in English) · 2026Article
- Covalent chemical probes.Communications chemistry · 2025Article
- Advances in sulfonyl exchange chemical biology: expanding druggable target space.Chemical science · 2025Review
- Rhodium-catalysed connective synthesis of diverse reactive probes bearing S(VI) electrophilic warheads.Beilstein journal of organic chemistry · 2025Article
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Authors and funding
7 authors.
Funding
Abstract
Sets of electrophilic probes are generally prepared using a narrow toolkit of robust reactions, which tends to limit both their structural and functional diversity. A unified synthesis of skeletally-diverse sulfonyl fluorides was developed that relied upon photoredox-catalysed dehydrogenative couplings between hetaryl sulfonyl fluorides and hydrogen donor building blocks. A set of 32 diverse probes was prepared, and then screened against Trypanosoma brucei. Four of the probes were found to have sub-micromolar anti-trypanosomal activity. A chemical proteomic approach, harnessing an alkynylated analogue and broad-spectrum fluorophosphonate tools, provided insights into the observed anti-trypanosomal activity, which likely stems from covalent modification of multiple protein targets. It is envisaged that the unified diversity-oriented approach may enable the discovery of electrophilic probes that have value in the elucidation of biological and biomedical mechanisms.
Identifiers
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Registered trials
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