Preparation, carbonic anhydrase enzyme inhibition and antioxidant activity of novel 7-amino-3,4-dihydroquinolin-2(1H)-one derivatives incorporating mono or dipeptide moiety

J Enzyme Inhib Med Chem. 2020 Dec;35(1):1021-1026. doi: 10.1080/14756366.2020.1751620.

Abstract

New dipeptide-dihydroquinolinone derivatives were successfully synthesised by benzotriazole mediated nucleophilic acyl substitution reaction and their structures were elucidated by spectroscopic and analytic techniques. The carbonic anhydrase (CA, EC 4.2.1.1) inhibitory activity of the new compounds was determined against four human (h) isoforms, hCA I, hCA II, hCA IX and hCA XII. While all compounds showed moderate to good in vitro CA inhibitory properties against hCA IX and hCA XII with inhibition constants in the micromolar level (37.7-86.8 and 2.0-8.6 µM, respectively), they did not show inhibitory activity against hCA I and hCA II up to 100 µM concentration. The antioxidant capacity of the peptide-dihydroquinolinone conjugates was determined using 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging method. Most of the synthesised compounds showed low antioxidant activities compared to the control antioxidant compounds BHA and α-tocopherol.

Keywords: Dipeptide; antioxidant; carbonic anhydrase; dihydroquinolinone derivatives.

MeSH terms

  • Antioxidants / chemical synthesis
  • Antioxidants / chemistry
  • Antioxidants / pharmacology*
  • Biphenyl Compounds / antagonists & inhibitors*
  • Carbonic Anhydrase Inhibitors / chemical synthesis
  • Carbonic Anhydrase Inhibitors / chemistry
  • Carbonic Anhydrase Inhibitors / pharmacology*
  • Carbonic Anhydrases / metabolism*
  • Dipeptides / chemistry
  • Dipeptides / pharmacology*
  • Dose-Response Relationship, Drug
  • Humans
  • Isoenzymes / antagonists & inhibitors
  • Isoenzymes / metabolism
  • Molecular Structure
  • Picrates / antagonists & inhibitors*
  • Quinolones / chemical synthesis
  • Quinolones / chemistry
  • Quinolones / pharmacology*
  • Structure-Activity Relationship

Substances

  • Antioxidants
  • Biphenyl Compounds
  • Carbonic Anhydrase Inhibitors
  • Dipeptides
  • Isoenzymes
  • Picrates
  • Quinolones
  • dihydroquinolin-2(1H)-one
  • 1,1-diphenyl-2-picrylhydrazyl
  • Carbonic Anhydrases

Grants and funding

The authors thank Inönü University, Turkey [BAPB – Grand No. FYL-2018–909], Universitá degli Studi di Firenze, Italy and the Italian Ministry for University and Research, MIUR for a grant to CTS [PRIN: rot. 2017XYBP2R].