Catalyst-Free, One-Pot, Three-Component Synthesis of 5-Amino-1,3-diphenyl-1H-pyrazole-4-carbonitriles in Green Media, and Evaluation of Their Biological Activities.

Objective: The tandem Knoevenagel-cyclocondensation reaction of aromatic aldehydes, malonitrile, and phenylhydrazine in water and ethanol at room temperature is described as an effective, one-pot, threecomponent synthesis of many scientifically relevant heterocyclic compounds. Methods: As a part of our efforts, we have synthesized pyrazole-4-carbonitriles and characterized using various spectroscopic methods and subjected for antimicrobial analysis. Results and Discussion: From our analysis, we observed best in vitro candidate as 5-amino-3-(2,5-difluorophenyl)-1-phenyl-1H-pyrazole-4-carbonitrile. The molecular docking analysis on common bacterial target suggested the involvement of 2,2-dialkylglycine decarboxylase (PDB ID: 1D7U) as a target for compound (IVi) (docking score: –9.32 kcal/mol). Furthermore, a molecular dynamic simulation of 100 ns resulted in the stability of best docked candidate, (IVi): 1D7U. Conclusions: We propose that best docked candidate, (IVi) as potential antimicrobial agents. [ABSTRACT FROM AUTHOR]