Discovery of a potent angiotensin converting enzyme inhibitor via virtual screening

Bioorg Med Chem Lett. 2017 Aug 15;27(16):3688-3692. doi: 10.1016/j.bmcl.2017.07.016. Epub 2017 Jul 5.

Abstract

Prompted by the prominent role of angiotensin converting enzyme (ACE) in hypertension, heart failures, myocardial infarction and diabetic nephropathy, we have attempted to discover novel ACE inhibitors through ligand-based virtual screening. Molecular docking method and rigorously validated model was utilized to search a natural compounds database. Finally, 36 compounds were randomly selected and subjected to in vitro ACE kinase inhibitory assay using fluorescence assays method. The results showed that three compounds (Licochalcone A, Echinatin and EGCG) have strong potential to be developed as a new class of ACE inhibitors. Further chemical modification via fragment modifications guided by structure and ligand-based computational methodologies can lead to discover better agents as potential clinical candidates.

Keywords: ACE; Angiotensin converting enzyme; Drug discovery; In silico; Virtual screening.

MeSH terms

  • Angiotensin-Converting Enzyme Inhibitors / chemistry*
  • Angiotensin-Converting Enzyme Inhibitors / metabolism
  • Binding Sites
  • Catechin / analogs & derivatives
  • Catechin / chemistry
  • Catechin / metabolism
  • Chalcones / chemistry
  • Chalcones / metabolism
  • Drug Evaluation, Preclinical
  • Humans
  • Molecular Docking Simulation
  • Peptidyl-Dipeptidase A / chemistry
  • Peptidyl-Dipeptidase A / metabolism*
  • Protein Binding
  • Protein Structure, Tertiary
  • Pyrrolizidine Alkaloids / chemistry
  • Pyrrolizidine Alkaloids / metabolism

Substances

  • Angiotensin-Converting Enzyme Inhibitors
  • Chalcones
  • Pyrrolizidine Alkaloids
  • echinatin
  • Catechin
  • epigallocatechin gallate
  • Peptidyl-Dipeptidase A
  • licochalcone A