期刊
PHARMACEUTICALS
卷 15, 期 4, 页码 -出版社
MDPI
DOI: 10.3390/ph15040477
关键词
carbonic anhydrase inhibitor; benzenesulfonamide; fluorescent thermal shift assay; X-ray crystallography; intrinsic thermodynamics of binding
资金
- European Union Structural Funds
- European Union Funds Investment Operational Program [01.2.2-CPVA-K-703-03-0006, 01.2.2-CPVA-K-703]
Novel benzenesulfonamide derivatives were synthesized and their binding to human carbonic anhydrase isozymes was determined. These compounds have potential applications in treating various illnesses, including glaucoma, altitude sickness, epilepsy, obesity, and cancer. The structures of some compounds and their binding mode in the enzyme's active site were elucidated.
A series of novel benzenesulfonamide derivatives were synthesized bearing Para-N beta,gamma-amino acid or para-N beta-amino acid and thiazole moieties and their binding to the human carbonic anhydrase (CA) isozymes determined. These enzymes are involved in various illnesses, such as glaucoma, altitude sickness, epilepsy, obesity, and even cancer. There are numerous compounds that are inhibitors of CA and used as pharmaceuticals. However, most of them bind to most CA isozymes with little selectivity. The design of high affinity and selectivity towards one CA isozyme remains a significant challenge. The beta and gamma amino acid-substituted compound affinities were determined by the fluorescent thermal shift assay and isothermal titration calorimetry for all 12 catalytically active human carbonic anhydrase isozymes, showing the full affinity and selectivity profile. The structures of several compounds were determined by X-ray crystallography, and the binding mode in the active site of CA enzyme was shown.
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