Synthesis of Novel Bis-pyrazole Derivatives as Antimicrobial Agents

Abstract

Bis-heterocycles especially those containing pyrazole moiety display much better antibacterial activity than mono heterocycles. Herein, we synthesised a series of new bis-pyrazoles and investigated their antimicrobial agents. A novel series of bis-pyrazole derivatives have been synthesized in good yield by coupling reaction of cyanoacetic acid {4-[(2-cyano-acetyl)-hydrazonomethyl]-benzylidene}-hydrazide with a number of diazonium salts of aromatic amines in DMF in the presence of NaOH. Refluxing of the produced hydrazones with hydrazine-hydrate in ethanolic solution afforded the respective bis-pyrazoles. On the other hand, the reaction of bis(cyanoacetic acid hydrazide) derivative with a diversity of hydrazonoyl chlorides in dioxane under reflux gave bis-pyrazoles. The structures of all the products were discussed and assured from all possible spectral data as well as for the elemental analysis. In addition, the results of the antimicrobial activity examination of selected derivatives revealed a high strength of some tested compounds compared to standard bactericides and fungicides utilized. Molecular docking of the newly synthesized compounds into the Enoyl ACP reductase active site supported the in vitro antimicrobial activity. All the tested compounds could fit in the enzyme binding pocket with significant binding affinities (-7.040 to -9.141 Kcal/mol). The good results of the antimicrobial examination of the newly synthesized bis-pyrazoles comprise the considerable evidence of the importance of bis-heterocyclic compounds which encourages us to continue designing and synthesising a novel series with potent biological activity in the future.