ABSTRACT: Human carbonic anhydrase (CA, EC 4.2.1.1) (hCA) isoforms I, II, IX, and XII were investigated for their inhibitory activity with a series of new Schiff’s bases based on quinazoline scaffold 4–27. The hCA I isoform was efficiently inhibited by Schiff’s bases 4–6, 10–19, 22–27 and had an inhibition constant (Ki) value of 52.8–991.7 nM compared with AAZ (Ki, 250 nM). Amongst the quinazoline derivatives, the compounds 2, 3, 4, 10, 11, 16, 18, 24, 26, and 27 were proven to be effective hCA II inhibitors, with Ki values of 10.8–52.6 nM, measuring up to AAZ (Ki, 12 nM). Compounds 2–27 revealed compelling hCA IX inhibitory interest with Ki values of 10.5–99.6 nM, rivaling AAZ (Ki, 25.0 nM). Quinazoline derivatives 3, 10, 11, 13, 15–19, and 24 possessed potent hCA XII inhibitory activities with KI
