Exploring benzoxaborole derivatives as carbonic anhydrase inhibitors: a structural and computational analysis reveals their conformational variability as a tool to increase enzyme selectivity. (1st January 2019)

• Record Type: Journal Article
• Authors: Langella, Emma; Alterio, Vincenzo; D'Ambrosio, Katia; Cadoni, Roberta; Winum, Jean-Yves; Supuran, Claudiu T.; Monti, Simona Maria; De Simone, Giuseppina; Di Fiore, Anna
• Is Part Of: Journal of enzyme inhibition and medicinal chemistry. Volume 34:Number 1(2019)
• Page Start: 1498
• Page End: 1505
• Publication Date: 2019-01-01
• Subjects: Carbonic anhydrase inhibitors -- benzoxaborole derivatives -- X-ray crystallography -- binding free energy calculations -- structure-based drug design; Enzyme inhibitors -- Periodicals; Enzyme Inhibitors -- periodicals; Biochemistry -- periodicals; 572.7
• DOI: 10.1080/14756366.2019.1653291
• Languages: English
• ISSNs: 1475-6366

Abstract

Abstract: Recent studies identified the benzoxaborole moiety as a new zinc-binding group able to interact with carbonic anhydrase (CA) active site. Here, we report a structural analysis of benzoxaboroles containing urea/thiourea groups, showing that these molecules are very versatile since they can bind the enzyme assuming different binding conformations and coordination geometries of the catalytic zinc ion. In addition, theoretical calculations of binding free energy were performed highlighting the key role of specific residues for protein-inhibitor recognition. Overall, these data are very useful for the development of new inhibitors with higher selectivity and efficacy for various CAs.