Abstract
Purpose: To synthesize new antimicrobial azo-pyrazolone derivatives III & IV and evaluate their antimicrobial activities using a combination of in vitro and molecular docking studies.
Methods: Azopyrazolone compounds were prepared from the reaction of substituted aniline diazonium with ethyl acetoacetate to give azoxobutyric acid derivatives (II) which were then reacted with phenyl hydrazine or hydrazine hydrate. The pyrazolone derivatives (IV) were acetylated with glacial acetic acid to yield new acetylated pyrazolones (V). An agar dilution method was used to demonstrate the antimicrobial activities of the pyrazolone derivatives and their minimum inhibitory concentration (MIC) values calculated. Molecular docking studies were employed to further evaluate the most active compounds (on the basis of the MICs obtained).
Results: The new pyrazolone derivatives showed varying antimicrobial activities (from negligible to strong) against a number of microorganisms. Derivatives IIIb and Vb showed potent activities against Bacillus subtilis, Sarcina lutea, Staphylococcus aureus and Enterococcus faecalis. However, the new compounds did not show antifungal activity. Molecular docking results for compounds Illb and Vb were consistent with their antimicrobial activities and proved that the compounds inhibited glucosamine-6phosph ate synth ase.
Conclusion: The new dichloropyrazolone compounds lila and Vb possess potent antimicrobial activities. These compounds have promising potential for use as new antibacterial agents or as templates for the design of new antimicrobial drugs.