Previously undescribed antioxidative O-heterocyclic angiotensin converting enzyme inhibitors from the intertidal seaweed Sargassum wightii as potential antihypertensives.

Four previously undescribed antioxidative O-heterocyclic analogues, characterized as 3″-isopropyl-3c-{3b-[(2-oxo-3,4-dihydro-2H-chromen-3-yl) methyl] butyl}-2″-butenyl-3'-hydroxy-2'-(2'b-methoxy-2'-oxoethyl)-3', 4'-dihydro-2H-pyran-4'-carboxylate (1), 2c-methylbutyl-6-[6c-(benzoyloxy)propyl]-6-methyl-tetrahydro-2H-pyran-2-carboxylate (2), 6-{6b-[3'-(5'a-methyl propyl)-3', 4'-dihydro-2H-pyran-6'-yl] ethyl}-tetrahydro-2H-pyran-2-one (3) and 7-(7c-methylpentyl)-hexahydro-2H-chromen-2-one (4) were isolated from the ethylacetate:methanol fraction of the brown seaweed Sargassum wightii. Nuclear magnetic resonance and mass spectroscopic experiments unambiguously attributed their structural identities. Antihypertensive activities of the studied compounds were determined in terms of their angiotensin converting enzyme (ACE) inhibitory potential. The 2H-pyranylcarboxylate derivative (1) displayed comparable activity (IC50 0.08 mg/mL) with standard antihypertensive agent captopril (IC50 0.07 mg/mL). The O-heterocyclic derivatives bearing 2H-pyran-4'-carboxylate (1) and 2H-pyran-2-carboxylate (2) frameworks showed significantly greater (p < 0.05) 1, 1-diphenyl-2-picryl-hydrazil radical quenching potential {IC50 (1) 0.34 and IC50 (2) 0.45 mg/mL} compared to the standard antioxidant α-tocopherol (IC50 0.63 mg/mL). Structure-activity relationship analyses demonstrated that the electronic and lipophilic descriptors might significantly contribute towards the target bioactivities of 2H-pyranylcarboxylates (1 and 2). Molecular docking simulations were carried out for ACE inhibition, and the binding energy obtained for the compounds (~7.04-8.48 kcal/mol) demonstrated their potential enzyme-ligand interactions. The potential of hitherto undescribed O-heterocyclic derivatives as natural antioxidant and antihypertensive functional food supplements and their utilization as therapeutic leads in the antihypertensive management were described in the present study.