Synthesis, molecular docking analysis, drug-likeness evaluation, and inhibition potency of new pyrazole-3,4-dicarboxamides incorporating sulfonamide moiety as carbonic anhydrase inhibitors.

Autor: Özkul Ş; Department of Biochemistry, Faculty of Arts and Sciences, Dumlupınar University, Kütahya, Turkey., Tunca E; Department of Biochemistry, Faculty of Arts and Sciences, Dumlupınar University, Kütahya, Turkey., Mert S; Department of Chemistry, Faculty of Arts and Sciences, Dumlupınar University, Kütahya, Turkey., Bayrakdar A; Vocational School of Higher Education for Healthcare Services, Iğdır University, Iğdır, Turkey., Kasımoğulları R; Department of Chemistry, Faculty of Arts and Sciences, Dumlupınar University, Kütahya, Turkey.
Jazyk: angličtina
Zdroj: Journal of biochemical and molecular toxicology [J Biochem Mol Toxicol] 2024 Apr; Vol. 38 (4), pp. e23704.
DOI: 10.1002/jbt.23704
Abstrakt: A series of novel pyrazole-dicarboxamides were synthesized from pyrazole-3,4-dicarboxylic acid chloride and various primary and secondary sulfonamides. The structures of the new compounds were confirmed by FT-IR, 1 H-NMR, 13 C-NMR, and HRMS. Then the inhibition effects of newly synthesized molecules on human erythrocyte hCA I and hCA II isoenzymes were investigated. K i values of the compounds were in the range of 0.024-0.496 µM for hCA I and 0.006-5.441 µM for hCA II. Compounds 7a and 7i showed nanomolar level of inhibition of hCA II, and these compounds exhibited high selectivity for this isoenzyme. Molecular docking studies were performed between the most active compounds 7a, 7b, 7i, and the reference inhibitor AAZ and the hCAI and hCAII to investigate the binding mechanisms between the compounds and the isozymes. These compounds showed better interactions than the AAZ. ADMET and drug-likeness analyses for the compounds have shown that the compounds can be used pharmacologically in living organisms.
(© 2024 Wiley Periodicals LLC.)
Databáze: MEDLINE
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