Synthesis, Molecular Docking, and Biological Evaluation of Some Novel Hydrazones and Pyrazole Derivatives as Anti‐inflammatory Agents

Abstract

2-Hydrazinyl-N-(4-sulfamoylphenyl)acetamide 3 was the key intermediate for the synthesis of novel hydrazones 4-10 and pyrazole derivatives 11-17. All compounds were tested for their in vivo anti-inflammatory activity and their ability to inhibit the production of PGE(2) in serum samples of rats. IC(50) values for the most active compounds for inhibition of COX-1 and COX-2 enzymes were determined in vitro, and they were also tested for their ulcerogenic effect. Molecular docking was performed on the active site of COX-2 to predict their mode of binding to the amino acids. Most of the synthesized compounds showed good anti-inflammatory activity especially compounds 3, 4, 8, 9, 15, and 17 which showed better activity than diclofenac as the reference drug. Compounds 3, 8, 9, 13, and 15-17 were less ulcerogenic than indomethacine as the reference drug. Most of the synthesized compounds interacted with Tyr 385 and Ser 530 in molecular docking study with additional hydrogen bond for compound 17. Compound 17 showed good selectivity index value of 11.1 for COX-1/COX-2 inhibition in vitro.

Design, synthesis and pharmacological evaluation of N -benzyl-piperidinyl-aryl-acylhydrazone derivatives as donepezil hybrids: Discovery of novel multi-target anti-alzheimer prototype drug candidates

“…Recent studies suggested that hydrazone derivatives display anti-inflammatory effects through the inhibition of cyclooxygenases 1 (COX-1) and 2 (COX-2) [50][51][52]. We selected compounds 4c and 4g, active in both AChE and anti-inflammatory assays, to evaluate their inhibition of COX-1 and COX-2 activity.…”

Synthesis and biological activity of hydrazones of o- and p-hydroxybenzoic acids. Spatial structure of 5-Bromo-2-hydroxybenzylidene-4-hydroxybenzohydrazide

“…For example, ftivazide, saluzide, and related drugs are used in the tuberculosis treatment [5,6]. Inhibitors of many enzymes like cyclooxygenase, monoaminoxidase, epoxide hydrolase, and various cathepsins have been prepared based on hydrazones [7][8][9][10][11]. Proteolytic enzymes cathepsin Е (EC 3.4.23.34) and elastase of neutrophil (EC 3.4.21.37) play important part in pathogenesis of autoimmune diseases and tumors growth [12][13][14].…”

Synthesis of new pyrazolo[3,4‐d]pyrimidine derivatives and evaluation of their anti‐inflammatory and anticancer activities

“…[25] It has been assumed by Regulski et al [26] that inflammation produces the appropriate conditions for genetic changes. Drugs containing pyrazole ring, the core scaffold in a number of selective COX-2 inhibitors [30][31][32][33][34][35][36][37][38][39][40][41] such as celecoxib and SC-558 (Scheme 1), [42,43] have been established as successful candidates for selective COX-2 inhibition. Oxidative stress may lead to DNA mutations resulting into uncontrolled proliferation and resistance to apoptosis.…”