First report of antioxidative 2H-chromenyl derivatives from the intertidal red seaweed Gracilaria salicornia as potential anti-inflammatory agents

Phytochemical investigation on biologically active compounds of an intertidal red seaweed Gracilaria salicornia (family Gracilariaceae) guided to the separation of two previously undisclosed 2H-chromenyl derivatives. The compounds were characterised as 4 '-[10 '-[7-hydroxy-2,8-dimethyl-6-(pentyloxy)-2H-chromen-2-yl]ethyl]-3 ',4 '-dimethyl-cyclohexanone (1) and 3 '-[10 '-(8-hydroxy-5-methoxy-2,6,7-trimethyl-2H-chromen-2-yl)ethyl]-3 '-methyl-2 '-methylene cyclohexyl butyrate (2) by extensive spectroscopic experiments. The studied metabolites recorded prospective bioactivities against 5-lipoxygenase (IC50 < 2.50 mM), whereas their selectivity indices were significantly greater (similar to 1) than ibuprofen (0.89) (p < 0.05), which attributed higher anti-inflammatory selectivity of 2H-chromenyl compounds against inducible cyclooxygenase-2 than its constitutive pro-inflammatory isoform of cyclooxygenase-1. The radical scavenging potential of 2 against oxidants, 2,2-diphenyl-1-picrylhydrazyl and 2,2 '-azino-bis-3 ethylbenzothiozoline-6-sulfonic acid were higher (IC50 < 1.35 mM) than standard antioxidant, alpha-tocopherol (IC50 1.42-1.79 mM). The greater hydrogen bond interactions and binding affinity of 2 (-7.35 kcal mol(-1)) bearing 2H-chromenyl ethyl-3 '-methyl-4 '-methylenecyclohexyl butyrate moiety with 5-lipoxygenase, along with higher electronic properties and permissible hydrophobic-hydrophilic balance, manifested towards its greater anti-inflammatory activity than 1.