Synthesis and Carbonic Anhydrase Inhibition Profiles of <i>N</i>-(3-sulfamoylphenyl)propanamide/benzamide Derivatives: Experimental and Computational Insights With Absorption, Distribution, Metabolism, and Excretion Profiling

Carbonic anhydrases (CA) I and II are the most abundant CA isozymes in erythrocytes and have been therapeutic targets in treating glaucoma, hypertension, ulcers, osteoporosis, and, neurological disorders. In this study, N-(3-sulfamoylphenyl) propanamide/benzamide derivatives were synthesized. Then, the CA isozymes were isolated and the inhibitory effects of the synthesized derivatives on these enzymes were investigated experimentally. The mechanism of inhibition was estimated by molecular docking studies. Finally, the Absorption, Distribution, Metabolism, and Excretion properties of derivatives were evaluated and analyzed in terms of pharmacokinetics and drug similarity. P4 was the most effective inhibitor among derivatives against both hCA-I and hCA-II with Ki constants as 0.22 +/- 0.01 and 0.33 +/- 0.05 mu M, respectively. Besides, P4 had a higher binding affinity to both enzymes with free binding energies of -8.14 and -8.03 kcal/mol. According to drug-likeness analysis, it was predicted that the derivatives comply with Lipinski's rule of five without any deviation.

Journal

CHEMISTRY & BIODIVERSITY

Year

2025

Volume

22

Issue

10

ISSN

1612-1872

eISSN

1612-1880

DOI

10.1002/cbdv.202403435

WoS UID

WOS:001497255900001