Tenerriside A, a Glycoside Variant From Sargassum tenerrimum, Exhibits Potent Angiotensin-Converting Enzyme (ACE) Inhibitory Activity.

Hypertension associated with elevated ACE activity highlights the need for exploring marine-derived bioactive compounds, particularly from brown seaweeds, as potential natural ACE inhibitors. A chemical study of specialized bioactive compounds from the brown seaweed Sargassum tenerrimum (family Sargassaceae) led to the isolation of an unprecedented glycoside, Tenerriside A, which was characterized as 8-((-14,16-dihydroxy-17-(hydroxymethyl)-4-((-20,21,22-trihydroxy-19-(hydroxymethyl)tetrahydro-2H-pyranyl)oxy)tetrahydro-2H-pyranyl)oxy)-13-(hydroxymethyl)pent-11-enyl heptanoate. Tenerriside A exhibited ACE inhibitory activity with an IC50 of 2.61 µM and exhibited strong antioxidant activity against free radicals (IC50 ∼21.67 µM), further supporting its potential anti-hypertensive efficacy. Electronic parameters, such as a topological polar surface area of 225.06 Å2, molecular polarizability of 54.47, may enhance recognition at the active enzyme site and lead to the effective inhibition of ACE and improved permeability across intermembrane barriers. Moreover, the low binding energy (-11.95 kcal/mol) and docking score (-14.15 kcal/mol) of Tenerriside A with the key amino acid residues in the ACE active site further support its anti-hypertensive bioactivity.