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

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 Schrodinger 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.

Automated summary

We synthesized and characterized N-substituted derivatives of 1-cyclopropyl-6,7-difluoro-8-methoxy-4-oxo-1,4-dihydroquinoline-3-carbohydrazide and evaluated their antibacterial activity. We found that modification at the C-3 position decreases the activity of the quinolone scaffold. Docking studies with S. aureus DNA gyrase confirmed the binding interaction of the most active molecule, 5a, and in silico ADME prediction showed that all synthesized compounds met the criteria for being orally active drugs.