Synthesis and Biological Potential Assessment of 2-Substituted Quinazolin-4(3H)-ones as Inhibitors of Phosphodiesterase-I and Carbonic Anhydrase-II

A library of twenty-five derivatives of 2-substituted quinazolin-4(3H)-ones 1-25 was synthesized and evaluated against phosphodiesterase-I (PDE) and carbonic anhydrase-II (CA). Compounds 17 (IC50 = 210.7 +/- 2.62 M), 16 (IC50 = 301.6 +/- 1.18 M), and 13 (IC50 = 458.13 +/- 3.60 M), selectively exhibited PDE inhibition while compounds 22 (IC50 = 61.33 +/- 2.38 M), 1 (IC50 = 108.30 +/- 0.93 M), and 21 (IC50 = 191.93 +/- 2.72 M), discriminatingly exhibited CA inhibition as compared to standards EDTA (IC50 = 277.69 +/- 2.52 M) and acetazolamide (IC50 = 0.12 +/- 0.03 M), for PDE and CA inhibitions, respectively. However, compound 15 was found to be active against both enzymes with the IC50 values 344.33 +/- 4.32 M and 20.94 +/- 0.58 M, for PDE and CA inhibitions, respectively. Remaining compounds were found to be inactive against both the enzymes. Structure-activity relationship studies are discussed herein.