Previously undisclosed bioactive sterols from corbiculid bivalve clam Villorita cyprinoides with anti-inflammatory and antioxidant potentials

Abstract

The estuarine Corbiculid bivalve black clam, Villorita cyprinoides collected from the Southwestern coastline regions of Arabian Sea are significant resources of nutritional and bioactive pluralities. The purification of ethyl acetate:methanol (EtOAc:MeOH) extract of V. cyprinoides characterized a previously undisclosed specialized abeo-pregnane-type sterol derivative 19 (10 → 5) abeo-20-methyl-pregn-10-en-3β-yl-hex-(3′E)-enoate (1) along with two cholestenols (22E),(241E)-241,242-dihomocholesta-5,22,241-trien-3β-ol (2) and (22E)-241-homocholesta-5,22-dien-(3β,241β)-diol (3). These compounds were characterized by comprehensive spectroscopic investigations. The anti-inflammatory (anti-cyclooxygenase-1, 2/5-lipoxidase) activities of 1 were considerably higher (IC50 < 1.10 mg/mL) than 2–3 (IC50 > 1.10 mg/mL). These studied compounds registered greater selectivity indices (∼1.03) against cyclooxygenase-2 than cyclooxygenase-1. The antioxidant property of abeo-pregnane-type sterol as determined by in vitro 2,2′-azino-bis-(3-ethyl-benzthiazoline-6-sulfonic acid) quenching potential was significantly greater (IC50 0.94 mg/mL) than those of substituted dihomocholesta-trien-ol (2) and homocholesta-dien-diol (3) (IC50 > 1.00 mg/mL). Structure-activity relationship studies demonstrated that bioactive potentials of the titled compounds were linearly related to their electronic factors along with optimum hydrophobic factors. In addition, molecular docking studies were performed in the active sites of COX-2 and their binding energies and docking scores were well correlated with in vitro anti-COX-2 potentials.