Synthesis and Activity Evaluation of Some Pyrazole-Pyrazoline Derivatives as Dual Anti-Inflammatory and Antimicrobial Agents

In this study, 18 pyrazole derivatives coupled with pyrazoline were synthesized and screened for their anti-inflammatory and antimicrobial activities. All the target compounds were synthesized smoothly and characterized using H-1 NMR, C-13 NMR, and HRMS. In vitro lipopolysaccharide (LPS)-induced tumor necrosis factor (TNF)-alpha model and in vivo xylene-induced ear-edema model were used to evaluate their anti-inflammatory activity. Antimicrobial activity against several Gram-positive strains and Gram-negative strains was evaluated using a serial dilution method. Pharmacological results indicated that most of the compounds markedly inhibited the expression of TNF-alpha at the concentration of 20 mu g/mL. Compounds 9b showed 66.4% inhibition for the LPS-induced TNF-alpha release, which was superior than that of the positive control drug dexamethasone (DXMS). And compounds 4a, 4b, 5a, 5b, 6b, and 9b showed comparable inhibition activity to DXMS. In xylene-induced ear-edema model, compound 4a inhibited edema by 48.71%, which was more effective than DXMS (47.18%) in inhibiting xylene-induced ear edema. Compound 4b, 5a, 5b, 6b, and 9b showed inhibition of 36.82%, 27.65%, 45.87%, 31.78%, and 43.67%, respectively. Furthermore, compounds 4a, 5a, 5b, and 9b displayed broad-spectrum antimicrobial activity against several Gram-positive and Gram-negative bacterial. These compounds, 4a, 5a, 5b, and 9b, possess both anti-inflammatory and antimicrobial activities, thus are worth further investigation to enhance their antimicrobial activities for the development of new class of dual anti-inflammatory-antimicrobial agents.