Antioxidative 2H-chromenyls attenuate pro-inflammatory 5-lipoxygenase and carbolytic enzymes: Prospective bioactive agents from Babylonidae gastropod mollusk Babylonia spirata.

Abstract

Oxygenated heterocycles are emerging as valuable pharmacophores involved in the prophylaxis and treatment of several diseases elicited by the reactive oxygen species. Bioassay-led chromatographic fractionation of the organic extract of the gastropod mollusk Babylonia spirata (family Babylonidae) yielded two unprecedented 2H-chromenyl derivatives characterized as 2-(butyryloxy)-5-hydroxy-hexahydro-2H-chromene-3-methyl carboxylate (1) and (3-hydroxy-hexahydro-2H-chromen-2-yl)methyl pentanoate (2). The chromenyl derivative (1) registered significantly greater attenuation potential against pro-inflammatory 5-lipoxygenase (IC50 ~2.02mM) than those exhibited by the compound (2) (IC50 2.76mM) and the non-steroidal anti-inflammatory drug ibuprofen (IC50 4.36mM, p<.05). The compound (1) exhibited comparable antioxidant activity (IC50 1.47-1.72mM) with standard antioxidative agent α-tocopherol (IC50 1.4-1.7mM). Inhibitory potential of chromenyl derivative (1) toward α-glucosidase (IC50 1.18mM) and α-amylase (IC50 0.92mM) was greater than those displayed by 2 (IC50 1.16-1.56mM). Structure-activity relationships revealed that bioactivities of the compounds were determined by the electronic factors and hydrophilic-lipophilic balance. PRACTICAL APPLICATIONS: The marine gastropod Babylonia spirata is one of the prominent edible gastropod species harvested from the coastlines along the southwestern region of the Indian peninsula. Two 2H-chromenyl derivatives were isolated to homogeneity from the organic extract of the marine buccinid gastropod B. spirata by the bioactivity-guided chromatographic fractionation and were found to possess potential antioxidant and attenuation properties against pro-inflammatory 5-lipoxygenase and carbolytic enzymes. The attenuation properties of the 2H-chromenyls against pro-inflammatory 5-lipoxygenase showed that 2H-chromenyl analogs possessed significantly greater anti-inflammatory potential than the non-steroidal anti-inflammatory drug ibuprofen. In particular, the chromenyl derivative bearing 2H-chromene-3-methyl carboxylate framework might constitute a prospective biogenic constituent in functional food and pharmaceutical applications for use against oxidative agents, including inflammation and hyperglycemic pathologies.