Previously undescribed antioxidative and anti-inflammatory chromenyls bearing 3H-isochromenone and furanyl-2H-chromenyl skeletons from the venerid clam, Paphia malabarica

Abstract

Previously undescribed chromenyl derivatives, characterized as 7-(2′-ethyl-1′-hydroxynonan-2′-yl)-6,7,8,8a-tetrahydro-3H-isochromen-1-(5H)-one (1) and 61-(3-((E)-31b-(furan-2′-yl)-prop-31b-en-31-yl)-4a,5,6,8a-tetrahydro-8-methyl-2H-chromen-6-yl)-ethyl-5′′-methyl-hexanoate (2) were isolated from ethyl acetate-methanol extract of yellow-foot bivalve clam, Paphia malabarica. Their structures have skeletons composed of isochromen-(5H)-one and furanyl-2H-chromenyl moieties, which are reported for the first time in marine organism. These were characterized by extensive one and two-dimensional nuclear magnetic resonance, infrared, and high-resolution mass spectroscopic experiments. The title compounds were evaluated for therapeutic potentials with regard to anti-inflammatory and antioxidant properties compared to known standards. These compounds exhibited comparable 2, 2-diphenyl-1-picrylhydrazyl (DPPH) and 2, 2′-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid) (ABTS+) radical scavenging activities with α-tocopherol (IC50 ~0.6–0.7 mg/mL). The significantly higher anti-5-lipoxygenase activity of the title compounds (IC50 0.76–0.82 mg/mL) than ibuprofen (IC50 0.93 mg/mL) indicated their potential anti-inflammatory properties. The selectivity indices (IC50 anti-cyclooxygenase-1/IC50anti-cyclooxygenase-2) of compounds 1 (1.19) and 2 (1.31) well established its safety profiles as an anti-inflammatory when compared to known drug, ibuprofen (0.44). The target bioactivities of chromenyl derivatives were guided by hydrophobic and electronic parameters. These compounds can be used as potential bioactive leads in functional food and medicinal applications.