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
-
. The hCA I isoform was efficiently inhibited by Schiff's bases
-
,
-
,
-
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
,
,
,
,
,
,
,
,
, and
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
-
revealed compelling hCA IX inhibitory interest with Ki values of 10.5-99.6 nM, rivaling AAZ (Ki, 25.0 nM). Quinazoline derivatives
,
,
,
,
-
, and
possessed potent hCA XII inhibitory activities with K
values of 5.4-25.5 nM vs. 5.7 nM of AAZ. Schiff's bases
,
,
, and
represented attractive antitumor hCA IX carbonic anhydrase inhibitors (CAIs) with K
rates (22.0, 34.8, 49.2, and 45.3 nM, respectively). Compounds
,
,
,
,
,
,
, and
showed hCA I inhibitors on hCA IX with a selectivity index of 22.46-107, while derivatives
,
, and
showed selective hCA I inhibitors on hCA XII with a selectivity profile of 45.04-58.58, in contrast to AAZ (SI, 10.0 and 43.86). Compounds
,
,
-
,
-
, and
showed a selectivity profile for hCA II inhibitors over hCA IX with a selectivity index of 2.02-19.67, whereas derivatives
,
,
,
,
,
,
,
,
, and
showed selective hCA II inhibitors on hCA XII with a selectivity profile of 4.84-26.60 balanced to AAZ (SI, 0.48 and 2.10).