Screening of benzenesulfonamide in combination with chemically diverse fragments against carbonic anhydrase by differential scanning fluorimetry. (1st January 2020)

• Record Type: Journal Article
• Authors: Krasavin, Mikhail; Kalinin, Stanislav; Zozulya, Sergey; Gryniukova, Anastasiia; Borysko, Petro; Angeli, Andrea; Supuran, Claudiu T.
• Is Part Of: Journal of enzyme inhibition and medicinal chemistry. Volume 35:Number 1(2020)
• Page Start: 306
• Page End: 310
• Publication Date: 2020-01-01
• Subjects: Differential scanning fluorimetry -- thermal shift assay -- protein affinity -- carbonic anhydrase II -- fragment-based drug discovery -- primary sulphonamide -- zinc binding group; Enzyme inhibitors -- Periodicals; Enzyme Inhibitors -- periodicals; Biochemistry -- periodicals; 572.7
• DOI: 10.1080/14756366.2019.1698562
• Languages: English
• ISSNs: 1475-6366

Abstract

Abstract: The differential scanning fluorimetry (DSF) screening of 5.692 fragments in combination with benzenesulfonamide (BSA) against bovine carbonic anhydrase ( b CA) delivered >100 hits that either caused, on their own, a significant thermal shift (Δ Tm, °C) in the protein melting temperature or significantly influenced the thermal shift observed for BSA alone. Three hits based on 1, 2, 3-triazole moiety represent the periphery of the recently reported potent inhibitors of h CA II, IX and XII which were efficacious in vivo . Such a re-discovery of suitable BSA periphery essentially validates the new fragment-based approach to the discovery of future CAIs. Structures of other validated fragment hits are reported. Graphical Abstract: UF0001