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

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 P_ow 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.

Graphical Abstract

Keywords:

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

Acknowledgements

The authors thank the Director, ICAR-CMFRI, and Head, Marine Biotechnology Division of ICAR-CMFRI for guidance and support.

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

This work was funded by the Indian Council of Agricultural Research (ICAR), New Delhi, India under Central Marine Fisheries Research Institute (ICAR-CMFRI) supported project “Development of Bioactive Pharmacophores from Marine Organisms” (grant number MBT/HLT/SUB23).