Background:
bis-heterocycles especially those containing pyrazole moiety display much
better antibacterial activity than mono heterocycles.
Objective:
Herein, we synthesised a series of new bis-pyrazoles and investigated their antimicrobial
agents.
Methods:
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.
Results:
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).
Conclusion:
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.