Antibacterial Activity of Novel 1-Cyclopropyl-6,7-Difluoro-8-Methoxy-4-Oxo-1,4-Dihydroquinoline-3-Carbohydrazide Derivatives

Abstract

We have synthesized and characterized N-substituted-1-cyclopropyl-6,7-difluoro-8-methoxy-4-oxo-1,4-dihydroquinoline-3-carbohydrazide derivatives and were evaluated for their antibacterial activity against Staphylococcus Aureus, Micrococcus Luteus, Bacillus subtilis and Gram-negative Escherichia Coli, Pseudomonas aeruginosa and Flavobacterium Devorans pathogens and found that any modification is done at C-3 position then the activity of quinolone scaffold is decreased. This shows that presence of carboxylic acid group at C-3 position is very important for antibacterial activities. To gain more molecular insight into the binding interaction of the synthesized compounds, docking studies with to S. aureus DNA gyrase (PDB: 2XCT) were conducted. Based on its potential anti-bacterial properties, the most active molecule, 5a, was submitted to molecular docking simulations using Schrödinger Glide software. The fluoroquinolones mechanism of action is entirely compatible with the binding interaction of the compound 5a. Further, all the synthesized compounds tested for In Silico ADME prediction and observed that all the compounds followed the criteria for orally active drug and therefore, these compounds can be further developed an oral drug candidate.

Keywords:

• Antibacterial
• quinoline-3-carbohydrazide
• gatifloxacin
• ciprofloxacin
• ADME prediction

Acknowledgements

The authors are very thankful to the Management, Principal and Head of Dept. of Chemistry, JET’s Z. B. Patil College, Dhule for providing the lab facilities and for encouragement. The authors are also thankful to Dr. Ulhas Patil, Head and Assistant Professor of R. C. Patel A. S. C. College, Shirpur (Dist Dhule) for testing antimicrobial activity of synthesized compounds.

Disclosure statement

No potential conflict of interest was reported by the author(s).