Computational Studies and Biological Evaluation on Synthesized Lead 1,3- diphenyl-4,5-dihydro-1H-pyrazole Moiety as Anti-Infective Agents

Background: Chronic non-communicable diseases were interlinked with inflammation, and infections should respond to the core of major diseases in both acute and chronic conditions. In drug discovery, developing a drug that acts as an anti-infective agent (anti-microbial and antiinflammatory) must be ideal and challenging for managing many chronic diseases. Objective: In this study, six lead pyrazoline hybrids were synthesized by cyclization of chalcones and characterized by various spectroscopic and elemental analyses. All synthesized compounds were screened for anti-inflammatory and anti-microbial activity by computational tools and biological evaluation. Methods: Synthesized pyrazoline analogues were characterized by various spectroscopic techniques and evaluated for prediction of pharmacokinetics, physicochemical properties and Molecular docking studies of various targeted enzymes on microbial and inflammatory mediators. Those compounds were screened by anti-microbial and anti-inflammatory activities by several in-vitro and in-vivo methods. Results: The synthesized compounds (A1-A6) were screened for anti-inflammatory activity in which compound A2 produced effective percentage inhibition (45.8 %) potent activity compared with that of standard indomethacin (49.7 %) in the carrageenan paw edema method were observed. The anti-microbial activity was screened on synthesized compounds, among which A3 [2-(1,3- diphenyl-4,5-dihydro-1H-pyrazol-5-yl) phenol, A2 [5-(4-chlorophenyl)-1,3-diphenyl-4,5-dihydro- 1H-pyrazole] produced potential percentage zone of inhibition between 80 - 70 % for bacterial strains and 94 - 89 % for fungal strains were observed. The minimum inhibitory concentration values of those compounds were 1.56 to 6.25 μg/ml for bacterial strains, and 1.56 to 12.5 μg/ml for fungal strains were noted compared with the standard gatifloxacin and clotrimazole, respectively. The molecular docking, pharmacokinetics and toxicity predictions on those compounds were supported further for developing potent anti-infective agents. Conclusion: The hypothesis of this research was correlated with the results of anti-inflammatory and anti-microbial activity. The binding interactions of respective enzymes coincided with a reduction of paw edema in the anti-inflammatory model and a zone of inhibition in anti-microbial activity.