Beta and Gamma Amino Acid-Substituted Benzenesulfonamides as Inhibitors of Human Carbonic Anhydrases

Abstract

A series of novel benzenesulfonamide derivatives were synthesized bearing para-N β,γ-amino acid or para-N β-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.

Synthesis of novel sulphamethoxazole derivatives and exploration of their anticancer and antimicrobial properties

“…In the light of the above facts and due to the huge development in antimicrobial activities of sulfamethoxazole derivatives, as well as in the continuation of our works in the field of the synthesis and investigation of various sulfonamides [40][41][42][43][44][45] we have synthesized a series of completely new unpublished sulfamethoxazole-based derivatives and have screened them against cancer cell and several standard bacteria and fungus to study their potential in search of novel anticancer and antimicrobial compounds.…”