Abstract

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 µM), 16 (IC₅₀ = 301.6 ± 1.18 µM), and 13 (IC₅₀ = 458.13 ± 3.60 µM), selectively exhibited PDE inhibition while compounds 22 (IC₅₀ = 61.33 ± 2.38 µM), 1 (IC₅₀ = 108.30 ± 0.93 µM), and 21 (IC₅₀ = 191.93 ± 2.72 µM), discriminatingly exhibited CA inhibition as compared to standards EDTA (IC₅₀ = 277.69 ± 2.52 µM) and acetazolamide (IC₅₀ = 0.12 ± 0.03µM), 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 µM and 20.94 ± 0.58 µM, for PDE and CA inhibitions, respectively. Remaining compounds were found to be inactive against both the enzymes. Structure-activity relationship studies are discussed herein.

Keywords: 2-Substituted quinazolin-4(3H)-ones, NPP1/Phosphodiesterase-I, Carbonic Anhydrase-II, Structure-Activity Relationship.

Graphical Abstract