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

Med Chem. 2015;11(4):336-41. doi: 10.2174/1573406410666141203123926.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetazolamide / chemistry
  • Animals
  • Carbonic Anhydrase II / antagonists & inhibitors*
  • Carbonic Anhydrase II / chemistry
  • Carbonic Anhydrase II / isolation & purification
  • Carbonic Anhydrase Inhibitors / chemical synthesis*
  • Carbonic Anhydrase Inhibitors / chemistry
  • Drug Design
  • Edetic Acid / chemistry
  • Enzyme Assays
  • Molecular Structure
  • Phosphodiesterase I / antagonists & inhibitors*
  • Phosphodiesterase I / chemistry
  • Phosphodiesterase I / isolation & purification
  • Phosphodiesterase Inhibitors / chemical synthesis*
  • Phosphodiesterase Inhibitors / chemistry
  • Quinazolinones / chemical synthesis*
  • Quinazolinones / chemistry
  • Small Molecule Libraries / chemical synthesis*
  • Small Molecule Libraries / chemistry
  • Snakes / metabolism
  • Solutions
  • Structure-Activity Relationship

Substances

  • Carbonic Anhydrase Inhibitors
  • Phosphodiesterase Inhibitors
  • Quinazolinones
  • Small Molecule Libraries
  • Solutions
  • Edetic Acid
  • Phosphodiesterase I
  • Carbonic Anhydrase II
  • Acetazolamide