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

Abstract

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 (∼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, α-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.

Graphical Abstract

Keywords:

• Gracilaria salicornia
• Gracilariaceae
• 2H-chromenyl derivatives
• antioxidant
• anti-inflammatory
• pro-inflammatory cyclooxygenase and lipoxygenase

Disclosure statement

The authors have no conflict of interest.

Additional information

Funding

The work was supported by Science and Engineering Research Board (SERB) grant (grant number SR/S1/OC-96A/2012) of the Department of Science and Technology, New Delhi, India. The authors thank the Director, Indian Council of Agricultural Research-Central Marine Fisheries Research Institute (ICAR-CMFRI), and Head, Marine Biotechnology Division, ICAR-CMFRI for guidance and support.