Novel furanyl derivatives from the red seaweed Gracilaria opuntia with pharmacological activities using different in vitro models

Abstract

Two previously undescribed furanyl compounds, characterized as 5-(7-(5-ethyl-3,4-dimethoxycyclooctyl) benzofuran-6-yl)-7-methyl-3,4,7,8-tetrahydro-2H-oxocin-2-one (compound 1) and 2-(3-ethyl-9-(2-methoxyethoxy)-1-oxo-2,3,4,9-tetrahydro-1H-xanthen-2-yl) ethyl-5-hydroxy-9-methoxy-7,8-dimethyl-8-(5-methylfuran-2-yl) nona-3,6-dienoate (compound 2) were derived from the ethyl acetate–methanol (EtOAc:MeOH) crude extract of red seaweed Gracilaria opuntia. The isolated compounds are the first furanyl natural products featuring methoxycyclooctyl benzofuran with tetrahydro-2H-oxocin framework and tetrahydro-1H-xanthenyl methoxy methylfuran skeletons. These compounds were assessed for anti-inflammatory activities against pro-inflammatory cyclooxygenase-2/5-lipoxygenase (COX-1, 2, and 5-LOX) and antioxidative effects in various in vitro models. The methylfuran derivative exhibited comparable inhibitory activities towards 5 LOX (IC50 0.209 × 10−2 M) with synthetic non-steroidal anti-inflammatory drugs (NSAID) ibuprofen (IC50 0.451 × 10−2 M, P 0.146 × 10−2 M), and were similar to those displayed by the synthetic antioxidants (butylated hydroxytoluene (BHT)/ butylated hydroxyanisole (BHA) (IC50 ~0.144–0.189 × 10−2 M, P < 0.05). The anti-inflammatory selectivity indices of the isolated compounds recorded significantly greater values (SI: anti-COX-1IC50/anti-COX-2IC50 ~1.08–1.09) than NSAIDs (aspirin, and ibuprofen, SI: 0.02 and 0.44, respectively, P < 0.05), and consequently, appeared to be safer. The isolated compounds showed significant anti-diabetic properties as determined by α-amylase/α-glucosidase (IC50 < 0.052 × 10−2 M) and dipeptidyl peptidase-4 (DPP-4, IC50 < 0.002 × 10−2 M) inhibitory activities. The angiotensin converting enzyme-I (ACE-I) inhibitory activity of the compounds (IC50 0.023–0.024 × 10−2 M) was found to be comparable with that recorded by commercial ACE inhibitor, captopril (IC50 0.037 × 10−2 M).