Callypyrones from marine Callyspongiidae sponge Callyspongia diffusa: antihypertensive bis- γ-pyrone polypropionates attenuate angiotensin-converting enzyme

Nat Prod Res. 2021 Dec;35(24):5801-5812. doi: 10.1080/14786419.2020.1837819. Epub 2020 Nov 2.

Abstract

Angiotensin I-converting enzyme (ACE) catalyses the biosynthesis of angiotensin II, a potent blood vessel constrictor, from angiotensin I, and ACE inhibitors were recognised as medications for hypertension. Undescribed bis-γ-pyrone polypropionate compounds, callypyrones A and B were purified from the organic extract of Callyspongiidae sponge species Callyspongia diffusa by repeated chromatographic purification. Callypyrone A exhibited significantly greater attenuation potential against ACE (IC50 0.48 mM) than that displayed by callypyrone B (IC50 0.57 mM) and showed comparable activity with standard ACE inhibitor captopril (IC50 0.36 mM). Higher electronic parameters of callypyrone A (topological surface area of 108.36) combined with balanced hydrophilic-lipophilic parameter (octanol-water coefficient, log Pow 1.9), as deduced from the structure-activity relationship analyses, could further indicate the improved ligand-receptor interactions resulting in its prospective ACE inhibitory activity. In silico docking analyses of the callypyrones with ACE recorded lowest binding energy (-12.58 kcal mol-1) for callypyrone A, which further supported the antihypertensive potential of the compound.

Keywords: Callyspongia diffusa; Callyspongiidae; angiotensin-converting enzyme; antihypertensive activity; bis-γ-pyrone polypropionate; callypyrones A-B; ligand–receptor interactions.

MeSH terms

  • Angiotensin-Converting Enzyme Inhibitors / pharmacology*
  • Animals
  • Antihypertensive Agents* / pharmacology
  • Callyspongia* / chemistry
  • Molecular Docking Simulation
  • Propionates / pharmacology*
  • Prospective Studies
  • Pyrones / pharmacology*

Substances

  • Angiotensin-Converting Enzyme Inhibitors
  • Antihypertensive Agents
  • Propionates
  • Pyrones