Design, synthesis and biological evaluation of N-(5-methyl-isoxazol-3-yl/1, 3, 4-thiadiazol-2-yl)-4-(3-substitutedphenylureido) benzenesulfonamides as human carbonic anhydrase isoenzymes I, II, VII and XII inhibitors. (2nd November 2016) - Mishra, Chandra Bhushan
Abstract: A series of N -(5-methyl-isoxazol-3-yl/1, 3, 4-thiadiazol-2-yl)-4-(3-substitutedphenylureido) benzenesulfonamide derivatives has been designed, synthesized and screened for their in vitro human carbonic anhydrase (hCA; EC 4.2.1.1) inhibition potential. These newly synthesized sulfonamide compounds were assessed against isoforms hCA I, II, VII and XII, with acetazolamide (AAZ) as a reference compound. The majority of these compounds were found quite weak inhibitor against all tested isoforms. Compound15 showed a modest inhibition potency against hCA I (Ki = 73.7 μM) and hCA VII (Ki = 85.8 μM). Compounds19 and25 exhibited hCA II inhibition with Ki values of 96.0 μM and 87.8 μM, respectively. The results of the present study suggest that, although the synthesized derivatives have weak inhibitory potential towards all investigated isoforms, some of them may serve as lead molecules for the further development of selective inhibitors incorporating secondary sulfonamide functionalities, a class of inhibitors for which the inhibition mechanism is poorly understood.