Abstract
Compounds 15, 45, 47, and 26 exhibited potent selective inhibitory activity against human isoforms CA I, II, IX, and XII (KIs: 39.4, 0.73, 1.6, and 5.2 nM, respectively), comparable to that of acetazolamide (AAZ) as a standard inhibitor (KI: 250.0, 12.0, 25.0, and 5.7 nM respectively).
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•Quinazoline-linked benzensulfonamides with CA inhibitory activity were synthesized.•Newly synthesized compounds potently inhibit human isoforms CA I, II, IX and XII.•Inhibitory activity of new compounds was comparable to that of CA inhibitor AAZ.•Compounds 14–15, 17, 19–21, 24–25, 28–29, 31, 35, 45, 47, 49&51 inhibit hCA I (KIs: 39.4–354.7 nM).•Compounds 15, 20, 24, 28, 29, 45, and 47 inhibit hCA II (KIs: 0.73–16.5 nM).•Compounds 13–29, 31–32, and 45–51 inhibit hCA IX (KIs: 1.6–32.2 nM).
Carbonic anhydrase (CA) inhibitory activities of newly synthesized quinazoline-linked benzensulfonamides 10–29, 31, 32, 35, 36, and 45–51 against human CA (hCA) isoforms I, II, IX, and XII were measured and compared to that of acetazolamide (AAZ) as a standard inhibitor. Potent selective inhibitory activity against hCA I was exerted by compounds 14, 15, 17, 19, 20, 21, 24, 25, 28, 29, 31, 35, 45, 47, 49, and 51 with inhibition constant (KIs) values of 39.4–354.7 nM that were nearly equivalent or even greater than that of AAZ (KI, 250.0 nM). Compounds 15, 20, 24, 28, 29, 45 and 47 proved to have inhibitory activities against hCA II with (KIs, 0.73–16.5 nM) that were similar or improved to that of AAZ (KI, 12.0 nM). Compounds 13–29, 31–32, and 45–51 displayed potent hCA IX inhibitory activities (KIs, 1.6–32.2 nM) that were more effective than or nearly equal to AAZ (KI, 25.0 nM). Compounds 14, 15, 20, 21, 26, 45, and 47 exerted potent hCA XII inhibitory activities (KIs, 5.2–9.2 nM), indicating similar CAI activities as compared to that of AAZ (KI, 5.7 nM).