Structural Docking Studies of COX-II Inhibitory Activity for Metabolites Derived from Corchorus olitorius and Vitis vinifera

Figures & data

TABLE 1 Effect of Quercetin metabolites as major components of C. olitorius and V. vinifera on cyclooxygenase (COX-I) and cyclooxygenase (COX-II) inhibitory activity

	COX-I inhibition			COX-II inhibition
	Mean	SEM	% Inhibition	Mean	SEM	% Inhibition
Co-extract	46.6	0.399	41%	53.31	0.49	62.4%
Quercetin-3-O –galactoside (Hypersoide) (25 µg/mL)	48.51	0.433	39.2%	51.48	0.471	60.7%
Vv extract	60.57	0.599	24.3%	39.42	0.502	49.2%
Quercetin 3-O-glucuronide (25 µg/mL)	49.84	0.420	37.6 %	50.15	0.370	60%

FIGURE 1 Overlay of the best scoring pose (left) for ibuprofen (A) and celecoxib (B) on their experimental crystal structures (right).

FIGURE 2 (Left): Superimposition of the active sites of both COX-I (cyano) and COX-II (magenta) showing the major structural differences resulting in a larger pocket in COX-II enzyme. (Right): COX-II active site consists of 3 main pockets: Pocket A formed of Phe367, Tyr371, Ser516, Trp373, and Leu370. Pocket B formed of Leu345, Arg106, Val102, Met99, Leu517, and Tyr341. Pocket C formed of Tyr341, Ser399, Phe504, Val509, and Leu338.

TABLE 2 Calculated docking scores for Quercetin metabolites into the active site of COX-I and COX-II enzymes

Metabolite	COX-I (kcal/mol)	COX-II (kcal/mol)
Quercetin	–7.0	–9.6
Quercetin 3’-Sulphate	–6.6	–8.3
3’-Methyl quercetin	–6.8	–9.5
Quercetin-7-glucuornide	–5.4	–5.0
Quercetin-4’-glucuornide	–4.5	–5.2

FIGURE 3 (Left): Quercetin and its metabolites docked inside COX-II active site. Quercetin (yellow), methyl quercetin (grey), quercetin sulphate (pink), and quercetin-7-glucuornide (green) all were able to bind to COX-II extra binding domain with the exception of quercetin-4-glucuornide (blue) which appears to be out of the pocket. (Right): Overlay of Celecoxib (grey), Quercetin (magenta), and Methyl quercetin (cyano) showing the benzopyran ring superimposed on the benzene sulphonamide moiety.

FIGURE 4 Crystal structure of benzopyran analogues SC-75416 (pink) and SD8381 (cyano) and 23d (magenta) together with the docked pose of quercetin (yellow) placed inside COX-II active site.