The Search for Cyclooxygenase-2 (COX-2) Inhibitors for the Treatment of Inflammation Disease: An in-silico Study

Figures & data

Table 1 The Pharmacophore Models

ID	Pharmacophore Model	Features of Pharmacophore	Goodness of Hit (GH)	AUC100%
NPX-1		2 hydrophobics, 3 h-bond acceptors, 1 negative ion	0.538	0.51
NPX-2		1 hydrophobic, 3 h-bond acceptors, 1 negative ion	0.302	0.50
NPX-3		2 hydrophobics, 2 h-bond acceptors, 1 negative ion	0.753	0.51
NPX-4		1 hydrophobic, 3 h-bond acceptors, 1 negative ion	0.253	0.51
NPX-5		2 hydrophobics, 2 h-bond acceptors, 1 negative ion	0.646	0.51
NPX-6		2 hydrophobics, 3 h-bond acceptors	0.037	0.50
NPX-7		2 hydrophobics, 3 h-bond acceptors, 1 negative ion	0.752	0.50
NPX-8		2 hydrophobics, 2 h-bond acceptors, 1 negative ion	0.754	0.51
NPX-9		2 hydrophobics, 2 h-bond acceptors, 1 negative ion	0.630	0.51
NPX-10		2 hydrophobics, 1 h-bond acceptors, 1 negative ion	0.693	0.51
NPX-11		1 hydrophobics, 1 h-bond acceptors, 1 negative ion	0.364	0.51
NPX-12		3 hydrophobics, 1 negative ion	0.751	0.50

Table 2 The Parameter and GH Score Obtained for Pharmacophore Model NPX-8

Parameter	Values
Total molecules in database (D)	13,585
Actives in database (A)	426
The obtained hits (Ht)	8
The obtained actives (Ha)	8
% actives [(Ha/Ht) x 100]	100
% actives to total molecules [(Ha/A) x 100]	1.877
Enrichment factor (E) [(Ha x D)/(Ht x A)]	31.889
False negatives [A - Ha]	418
False positives [Ht - Ha]	0
Goodness of Hit Score (GH)	0.754

Figure 1 Display the pharmacophore features of (R)-naproxen, in which hydrophobic, negative ion, and hydrogen bond acceptors were assigned as yellow, brown, and red arrows, respectively.

Figure 2 The area under curve (AUC) of receiver operating characteristic plot (ROC) of NPX-8.

Figure 3 (A) Superimposed of (R)-naproxen between X-ray (green) and docked (blue) conformations with RMSD 0.71 Å. (B) The interaction of (R)-naproxen in the cavity of COX-2.

Figure 4 The molecular structures of best-docked hit molecules.

Figure 5 The interactions of Lig_1805/ZINC103584272, Lig_553/ZINC408573132, Lig_680/ZINC103584263, and Lig_2006/ZINC19324645, each with COX-2.