Marginolides A-B, polyether macrolide analogues from veined octopus Amphioctopus marginatus: anti-hypertensive leads attenuate angiotensin-converting enzyme

Abstract

Angiotensin-I-converting enzyme (ACE) is considered as a major drug target for the treatment of hypertension as it catalyses the production of vasoconstrictor angiotensin II from angiotensin I. ACE inhibitor agents are an effective therapeutic strategy to control high blood pressure. Unprecedented polyether macrolides, marginolide A and B were isolated from the crude extract of marine octopus, Amphioctopus marginatus via bioassay-directed sequential chromatographic fractionation. Marginolide A displayed considerably greater ACE attenuation potential (IC₅₀ 0.58 mM) than that exhibited by marginolide B (IC₅₀ 0.72 mM). Higher antioxidant properties of marginolide A against the oxidant species (IC₅₀ ∼ 1 mM) also supported its potential ACE inhibitory activity. Higher polar characteristics along with acceptable hydrophobic-hydrophilic equilibrium (partition coefficient of octanol-water, log P_ow 2–4) revealed the potential anti-hypertensive activities of marginolides. This study recognized the anti-hypertensive properties of marginolides as promising pharmaceutical leads.

Graphical Abstract

Keywords:

• Marine octopus Amphioctopus marginatus
• polyether macrolides
• marginolides A-B
• anti-hypertensive
• angiotensin-converting enzyme

Disclosure statement

The authors declare no competing financial interest.

Data availability statement

The chromatographic and spectroscopic spectral data are included as supplementary item.

Additional information

Funding

The authors gratefully acknowledge the funding by the Indian Council of Agricultural Research (ICAR, New Delhi, India) (grant number MBT/HLT/SUB23). The authors are grateful to the Director, ICAR-CMFRI, and Head, Marine Biotechnology Division of ICAR-CMFRI for facilitating the research activities. The authors are thankful to the Chairman, Department of Chemistry, Mangalore University (Karnataka, India) for providing with the necessary support.