Benzimidazole design, synthesis, and docking to build selective carbonic anhydrase VA inhibitors

Publication date: Available online 24 December 2017
Source:Bioorganic & Medicinal Chemistry
Author(s): Edita Čapkauskaitė, Audrius Zakšauskas, Virginijus Ruibys, Vaida Linkuvienė, Vaida Paketurytė, Marius Gedgaudas, Visvaldas Kairys, Daumantas Matulis
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.

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