Journal
JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY
Volume 35, Issue 1, Pages 598-609Publisher
TAYLOR & FRANCIS LTD
DOI: 10.1080/14756366.2020.1722121
Keywords
Metalloenzyme; quinazolinone; sulphonamide; inhibition; selectivity; molecular docking study
Funding
- Deanship of Scientific Research at King Saud University [RG-1435-046]
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Inhibitory action of newly synthesised 4-(2-(2-substituted-thio-4-oxoquinazolin-3(4H)-yl)ethyl)benzenesulfonamides compounds 2-13 against human carbonic anhydrase (CA, EC 4.2.1.1) (hCA) isoforms I, II, IX, and XII, was evaluated. hCA I was efficiently inhibited by compounds 2-13 with inhibition constants (K(I)s) ranging from 57.8-740.2 nM. Compounds 2, 3, 4, and 12 showed inhibitory action against hCA II with K(I)s between 6.4 and 14.2 nM. CA IX exhibited significant sensitivity to inhibition by derivatives 2-13 with K-I values ranging from 7.1 to 93.6 nM. Compounds 2, 3, 4, 8, 9, and 12 also exerted potent inhibitory action against hCA XII (K(I)s ranging from 3.1 to 20.2 nM). Molecular docking studies for the most potent compounds 2 and 3 were conducted to exhibit the binding mode towards hCA isoforms as a promising step for SAR analyses which showed similar interaction with co-crystallized ligands. As such, a subset of these mercaptoquinazolin-4(3H)-one compounds represented interesting leads for developing new efficient and selective carbonic anhydrase inhibitors (CAIs) for the management of a variety of diseases including glaucoma, epilepsy, arthritis and cancer.
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