Spirornatas A-C from brown alga Turbinaria ornata: Anti-hypertensive spiroketals attenuate angiotensin-I converting enzyme

Abstract

Bioactive compounds with angiotensin-I converting enzyme attenuation potential are deemed as therapeutic agents for hypertension owing to their capacity to suppress the conversion of angiotensin-I into the vasoconstrictor angiotensin-II. In an aim to develop natural angiotensin-I converting enzyme (ACE-I) inhibitors from marine algae, three 6, 6-spiroketals, spirornatas A-C were isolated from the organic extract of the spiny brown marine macroalga Turbinaria ornata (Turner) (family Sargassaceae). Spirornata A exhibited comparatively greater ACE-I attenuation potential (IC50 4.5 μM) than those displayed by other studied spiroketals (IC50 4.7–4.9 μM), and its activity was comparable to the ACE inhibitory agent captopril (IC50 4.3 μM). Greater antioxidant properties of spirornata A against oxidants (IC50 1.1–1.3 mM) also substantiated its potential attenuation property against ACE-I. Structure-activity correlation studies showed that electronic properties (topological polar surface area, 71) and balanced hydrophilic-lipophilic parameters (partition coefficient of logarithmic octanol-water ∼3.2) of spirornata A appeared to play pivotal roles in the inhibition of the targeted enzyme. Predicted drug-likeness and other physicochemical parameters appeared to attribute to the acceptable oral bioavailability of spiroketal derivatives. Additionally, the least binding energy of spirornata A with ACE-I (−10.5 kcal/mol) coupled with the maximum number of hydrogen-bonding interactions with allosteric sites of the zinc-dependent dicarboxypeptidyl peptidase could recognize its potential therapeutic application against hypertensive diseases.