Exploration of Aromatic Hydrazides as Inhibitors of Human Carbonic Anhydrases.

ABSTRACT: A large set of hydrazide-based derivatives were explored as inhibitors of the human (h) carbonic anhydrase (CA) isoforms I, II, IV, IX, and XII. A wide series of compounds were synthesized and then assessed for their CA inhibitory activity using a CO₂ hydrase stopped-flow assay. Generally, these inhibitors demonstrated micromolar activity against the evaluated hCAs. Specifically, some derivatives bearing a ureido-linker exhibited the highest inhibitory potency, showing inhibition constants (K_Is) in the low-micromolar range against hCAs IV, XI, and XII. Moreover, two of them were detected as submicromolar inhibitors of isoform IV (K_Is: 0.8-0.96 µM). Molecular modeling was carried out to investigate the binding mode of the most selective and potent compounds

SUBMITTER: Menendez GB 

PROVIDER: S-EPMC11959329 | biostudies-literature | 2025 Apr

REPOSITORIES: biostudies-literature