Novel furanyl derivatives from the red seaweed <italic>Gracilaria opuntia</italic> with pharmacological activities using different in vitro models.

Two previously undescribed furanyl compounds, characterized as 5-(7-(5-ethyl-3,4-dimethoxycyclooctyl) benzofuran-6-yl)-7-methyl-3,4,7,8-tetrahydro-<italic>2H</italic>-oxocin-2-one (compound <bold>1</bold>) and 2-(3-ethyl-9-(2-methoxyethoxy)-1-oxo-2,3,4,9-tetrahydro-<italic>1H</italic>-xanthen-2-yl) ethyl-5-hydroxy-9-methoxy-7,8-dimethyl-8-(5-methylfuran-2-yl) nona-3,6-dienoate (compound <bold>2</bold>) were derived from the ethyl acetate-methanol (EtOAc:MeOH) crude extract of red seaweed <italic>Gracilaria opuntia</italic>. The isolated compounds are the first furanyl natural products featuring methoxycyclooctyl benzofuran with tetrahydro-<italic>2H</italic>-oxocin framework and tetrahydro-<italic>1H</italic>-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, <italic>P</italic> <italic><</italic> 0.05), which indicated its potential anti-inflammatory properties. The antioxidative properties of the furanyl derivatives as resolved by 1,1-diphenyl-2-picrylhydrazyl (DPPH) and 2,2ʹ-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid (ABTS) free radical scavenging activities were found to be significantly greater (IC₅₀ ~0.051-0.055 × 10⁻² M) than those exhibited by α-tocopherol (IC₅₀ > 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, <italic>P</italic> <italic><</italic> 0.05). The anti-inflammatory selectivity indices of the isolated compounds recorded significantly greater values (SI: anti-COX-1_IC50/anti-COX-2_IC50 ~1.08-1.09) than NSAIDs (aspirin, and ibuprofen, SI: 0.02 and 0.44, respectively, <italic>P</italic> <italic><</italic> 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). [ABSTRACT FROM AUTHOR]