Repurposing of World-Approved Drugs for Potential Inhibition against Human Carbonic Anhydrase I: A Computational Study.

ABSTRACT: Human carbonic anhydrases (hCAs) have enzymatic activities for reversible hydration of CO₂ and are acknowledged as promising targets for the treatment of various diseases. Using molecular docking and molecular dynamics simulation approaches, we hit three compounds of methyl 4-chloranyl-2-(phenylsulfonyl)-5-sulfamoyl-benzoate (84Z for short), cyclothiazide, and 2,3,5,6-tetrafluoro-4-piperidin-1-ylbenzenesulfonamide (3UG for short) from the existing hCA I inhibitors and word-approved drugs. As a Zn²⁺-dependent metallo-enzyme, the influence of Zn²⁺ ion models on the stability of metal-binding sites during MD simulations was addressed as well. MM-PBSA analysis predicted a strong binding affinity of -18, -16, and -14 kcal/mol, respectively, for these compounds,

SUBMITTER: Zheng N 

PROVIDER: S-EPMC10454238 | biostudies-literature | 2023 Aug

REPOSITORIES: biostudies-literature