Synthesis, in-vitro, in-vivo anti-inflammatory activities and molecular docking studies of acyl and salicylic acid hydrazide derivatives

Over the course of time several drugs have been synthesized and are available in market for the treatment of inflammation. However, they were unable to cure effectively and associated with side effects. To effectively deal with such diseases, heterocycles and their derivatives have gained their special position. For this reason 1,3,4-oxadiazole (15-16), 1,2,4-triazole (17-18), Schiff base (19-24) and 3,5-disubstituted pyrazole (25) derivatives were synthesized starting from salicylic acid and acyl acid hydrazides (12-14) as COX-1 and COX-2 inhibitors. In vivo anti-inflammatory activities were also tested by carrageenan-induced mice paw edema against albino mice of any sex. Structures of all the synthesized compounds were confirmed by FT-IR and ¹H NMR analysis. Schiff base derivative of 4-amiontirazole (24) with IC₅₀ value of 1.76 ± 0.05 (COX-2) and 117.8 ± 2.59 emerged as potent COX-2 Inhibitor. Furthermore, we also performed in-vivo anti-inflammatory investigations by using carrageenan induced paw edema test. From in-vivo anti-inflammatory activities, it was found that after 1 h the maximum percentage inhibition 15.8% was observed by compound 14 which is comparable with that of the standard drug followed by the compound 18 with percentage inhibition of 10.5%. After 3 h, the maximum percentage inhibition was observed by compound 18 with 22.2% and compound 14 with 16.7%. After 5 h the maximum percentage inhibition was observed by compound 18 with 29.4% followed by compound 16 with 23.5%. We further explore the mechanism of the inhibition by using docking simulations. Docking studies revealed that the selective COX-2 inhibitors established interactions with additional COX-2 Enzyme pocket residues.