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

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.