Benzimidazole design, synthesis, and docking to build selective carbonic anhydrase VA inhibitors. Issue 3 (1st February 2018)

• Record Type: Journal Article
• Authors: Čapkauskaitė, Edita; Zakšauskas, Audrius; Ruibys, Virginijus; Linkuvienė, Vaida; Paketurytė, Vaida; Gedgaudas, Marius; Kairys, Visvaldas; Matulis, Daumantas
• Is Part Of: Bioorganic & medicinal chemistry. Volume 26:Issue 3(2018)
• Page Start: 675
• Page End: 687
• Publication Date: 2018-02-01
• Subjects: Carbonic anhydrase isozyme I, II, III, IV, VA, VB, VI, VII, IX, XII, XIII, and XIV -- Fluorescent thermal shift assay -- ThermoFluor® -- Sulfonamide -- N-Alkylated benzimidazole -- Imidazole -- Indoline -- 3, 4-Dihydro-2H-quinoline -- CA inhibitor -- Docking; Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; Biochemistry -- Periodicals; Chemistry, Clinical -- Periodicals; Chemistry, Organic -- Periodicals; Chimie bio-organique -- Périodiques; Chimie pharmaceutique -- Périodiques; 615.19
• DOI: 10.1016/j.bmc.2017.12.035
• Languages: English
• ISSNs: 0968-0896

Abstract

Graphical abstract: Abstract: The similarity of human carbonic anhydrase (CA) active sites makes it difficult to design selective inhibitors for one or several CA isoforms that are drug targets. Here we synthesize a series of compounds that are based on 5-[2-(benzimidazol-1-yl)acetyl]-2-chloro-benzenesulfonamide (1a ) which demonstrated picomolar binding affinity and significant selectivity for CA isoform five A (VA), and explain the structural influence of inhibitor functional groups to the binding affinity and selectivity. A series of chloro-substituted benzenesulfonamides bearing a heterocyclic tail, together with molecular docking, was used to build inhibitors that explore substituent influence on the binding affinity to the CA VA isoform.