title: Synthesis and Biological Potential Assessment of 2-Substituted Quinazolin-4(3H)-ones as Inhibitors of Phosphodiesterase-I and Carbonic Anhydrase-II.
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 ± 0.03 µM), 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.
authors.forename: Syed Muhammad
authors.initials: SM
authors.lastname: Saad
authors.forename: Muhammad
authors.initials: M
authors.lastname: Saleem
authors.forename: Shahnaz
authors.initials: S
authors.lastname: Perveen
authors.forename: Muhammad Tanveer
authors.initials: MT
authors.lastname: Alam
authors.forename: Khalid Mohammed
authors.initials: KM
authors.lastname: Khan
authors.affiliation: H.E.J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi, Karachi-75270, Pakistan. khalid.khan@iccs.edu.
authors.forename: Muhammad Iqbal
authors.initials: MI
authors.lastname: Choudhary
mesh_terms: D000086:Acetazolamide / Q000737:chemistry; D000818:Animals; D024402:Carbonic Anhydrase II / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000302:isolation & purification; D002257:Carbonic Anhydrase Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry; D015195:Drug Design; D004492:Edetic Acid / Q000737:chemistry; D057075:Enzyme Assays; D015394:Molecular Structure; D043264:Phosphodiesterase I / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000302:isolation & purification; D010726:Phosphodiesterase Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry; D052999:Quinazolinones / Q000138:chemical synthesis* / Q000737:chemistry; D054852:Small Molecule Libraries / Q000138:chemical synthesis* / Q000737:chemistry; D012911:Snakes / Q000378:metabolism; D012996:Solutions; D013329:Structure-Activity Relationship
chemical_list: D002257:Carbonic Anhydrase Inhibitors; D010726:Phosphodiesterase Inhibitors; D052999:Quinazolinones; D054852:Small Molecule Libraries; D012996:Solutions; D004492:Edetic Acid; D043264:Phosphodiesterase I; D024402:Carbonic Anhydrase II; D000086:Acetazolamide