Figures & data
Figure 1. Chemical structures of certain reported antipyrine, oxadiazolyl, thiadiazolyl, pyrimidinyl analogues and our designed compounds (4,6,8).
![Figure 1. Chemical structures of certain reported antipyrine, oxadiazolyl, thiadiazolyl, pyrimidinyl analogues and our designed compounds (4,6,8).](/cms/asset/82f57c35-aaa2-46ba-a956-475c41ad3705/ienz_a_2162511_f0001_c.jpg)
Table 1. IC50 values of the tested compounds as COX inhibitors.
Figure 2. (A) Proposed binding interactions of compound 4b into COX-1 enzyme (PDB ID 6Y3C). (B) Proposed binding interactions 4b into COX-2 enzyme (PDB ID 5KIR). Important residues in the active site are indicated by lines, while the gray dotted lines are used for representing H-bonds. For the sake of clarity, nonpolar Hs were removed. In the ligand-interaction diagrams the magenta arrow represents the H-bond, the green line the π–π stacking, the red line the cation-π stacking.
![Figure 2. (A) Proposed binding interactions of compound 4b into COX-1 enzyme (PDB ID 6Y3C). (B) Proposed binding interactions 4b into COX-2 enzyme (PDB ID 5KIR). Important residues in the active site are indicated by lines, while the gray dotted lines are used for representing H-bonds. For the sake of clarity, nonpolar Hs were removed. In the ligand-interaction diagrams the magenta arrow represents the H-bond, the green line the π–π stacking, the red line the cation-π stacking.](/cms/asset/e2d013d0-549a-4187-88b8-77af0b56f627/ienz_a_2162511_f0002_c.jpg)
Figure 3. (A) Proposed binding interactions 4c into COX-1 enzyme (PDB ID 6Y3C). (B) Proposed binding interactions 4c into COX-2 enzyme. In the ligand-interaction diagrams the magenta arrow represents the H-bond, the green line the π–π stacking, the red line the cation-π stacking.
![Figure 3. (A) Proposed binding interactions 4c into COX-1 enzyme (PDB ID 6Y3C). (B) Proposed binding interactions 4c into COX-2 enzyme. In the ligand-interaction diagrams the magenta arrow represents the H-bond, the green line the π–π stacking, the red line the cation-π stacking.](/cms/asset/6eb1a183-72e4-4bc2-85b3-3c56617bbf79/ienz_a_2162511_f0003_c.jpg)
Figure 4. (A) Proposed binding interactions 6c into COX-1 enzyme (PDB ID 6Y3C). (B) Proposed binding interactions 6c into COX-2 enzyme. In the ligand-interaction diagrams the magenta arrow represents the H-bond, the green line the π–π stacking, the red line the cation-π stacking.
![Figure 4. (A) Proposed binding interactions 6c into COX-1 enzyme (PDB ID 6Y3C). (B) Proposed binding interactions 6c into COX-2 enzyme. In the ligand-interaction diagrams the magenta arrow represents the H-bond, the green line the π–π stacking, the red line the cation-π stacking.](/cms/asset/23a759c7-6dae-4d0b-b0bd-2853f38c294b/ienz_a_2162511_f0004_c.jpg)
Figure 5. (A) Proposed binding interactions 8d into COX-1 enzyme (PDB ID 6Y3C). (B) Proposed binding interactions 8d into COX-2 enzyme. In the ligand-interaction diagrams the magenta arrow represents the H-bond, the green line the π–π stacking, the red line the cation-π stacking.
![Figure 5. (A) Proposed binding interactions 8d into COX-1 enzyme (PDB ID 6Y3C). (B) Proposed binding interactions 8d into COX-2 enzyme. In the ligand-interaction diagrams the magenta arrow represents the H-bond, the green line the π–π stacking, the red line the cation-π stacking.](/cms/asset/b6f7951b-6921-40b3-84a9-026472b085b2/ienz_a_2162511_f0005_c.jpg)
Figure 6. Effects of celecoxib (CLX), 4 b, and 4c on carrageenan-induced paw edoema. *** p < 0.001 compared to the carrageenan group.
![Figure 6. Effects of celecoxib (CLX), 4 b, and 4c on carrageenan-induced paw edoema. *** p < 0.001 compared to the carrageenan group.](/cms/asset/3a2a4e3c-7f4f-44f7-93eb-7b273701199c/ienz_a_2162511_f0006_c.jpg)
Figure 7. (A) Representative images of hematoxylin-eosin-stained paw sections showing areas of inflammation (arrows). (B) Semi-quantitative scoring of inflammation. *** p < 0.001 compared to the control group; # p < 0.05 compared to the carrageenan group.
![Figure 7. (A) Representative images of hematoxylin-eosin-stained paw sections showing areas of inflammation (arrows). (B) Semi-quantitative scoring of inflammation. *** p < 0.001 compared to the control group; # p < 0.05 compared to the carrageenan group.](/cms/asset/9470987b-5661-496e-b428-89f3031b9282/ienz_a_2162511_f0007_c.jpg)
Figure 8. (A) Representative images of immunostained paw sections showing NF-κB positive expression (arrows). (B) Semi-quantitative scoring of NF-κB positive expression. *** p < 0.001 in comparison to the control group; # p < 0.05 compared to the carrageenan group.
![Figure 8. (A) Representative images of immunostained paw sections showing NF-κB positive expression (arrows). (B) Semi-quantitative scoring of NF-κB positive expression. *** p < 0.001 in comparison to the control group; # p < 0.05 compared to the carrageenan group.](/cms/asset/0e43aca1-87cd-4797-a8fb-17d4c1f7bb68/ienz_a_2162511_f0008_c.jpg)
Figure 9. (A) Representative images of immunostained paw sections showing COX-2 positive expression (arrows). (B) Semi-quantitative scoring of COX-2 positive expression. *** p < 0.001 compared to the control group; # p < 0.05, ## P < 0.01 compared to the carrageenan group.
![Figure 9. (A) Representative images of immunostained paw sections showing COX-2 positive expression (arrows). (B) Semi-quantitative scoring of COX-2 positive expression. *** p < 0.001 compared to the control group; # p < 0.05, ## P < 0.01 compared to the carrageenan group.](/cms/asset/4bbe41b6-15db-4f97-a0af-959cdcdf7440/ienz_a_2162511_f0009_c.jpg)
Figure 10. Effects of Celecoxib (CLX), 4 b, and 4c on carrageenan-induced elevation of (A) Prostaglandin E2 (PGE2) and (B) Tumour necrosis factor-alpha (TNF-α) paw tissue levels. *** p < 0.001 compared to the control group; # p < 0.05, ### P < 0.001 compared to the carrageenan group; $$p < 0.01, $$$P < 0.001 compared to the CLX group; + p < 0.05 compared to the 4 b group.
![Figure 10. Effects of Celecoxib (CLX), 4 b, and 4c on carrageenan-induced elevation of (A) Prostaglandin E2 (PGE2) and (B) Tumour necrosis factor-alpha (TNF-α) paw tissue levels. *** p < 0.001 compared to the control group; # p < 0.05, ### P < 0.001 compared to the carrageenan group; $$p < 0.01, $$$P < 0.001 compared to the CLX group; + p < 0.05 compared to the 4 b group.](/cms/asset/ccfb5ff9-a220-44ee-9208-1cc917bc6027/ienz_a_2162511_f0010_b.jpg)
Figure 11. Effects of Celecoxib (CLX), 4 b, and 4c on carrageenan-induced elevation of (A) malondialdehyde (MDA) and (B) Nitric oxide (NO) paw tissue contents. ** p < 0.01, *** p < 0.001 compared to the control group; # p < 0.05, ### P < 0.001 compared to the carrageenan group; $$p < 0.01 compared to the CLX group; + p < 0.05 compared to the 4 b group.
![Figure 11. Effects of Celecoxib (CLX), 4 b, and 4c on carrageenan-induced elevation of (A) malondialdehyde (MDA) and (B) Nitric oxide (NO) paw tissue contents. ** p < 0.01, *** p < 0.001 compared to the control group; # p < 0.05, ### P < 0.001 compared to the carrageenan group; $$p < 0.01 compared to the CLX group; + p < 0.05 compared to the 4 b group.](/cms/asset/93b675b0-b6da-491c-bdf3-d4a0e783ed85/ienz_a_2162511_f0011_b.jpg)