Synthesis, Characterization, and Antibacterial Effectiveness of Gemifloxacin C-3 Modified Amide Analogs: A Theoretical and Experimental Approach

Abstract

In search of a newer, efficient, and adaptable antimicrobial solution to combat the resistance that has developed due to the widespread extensive and in appropriate use of antibiotics. Seven new amide analogs of Gemifloxacin (G-D01-G-D07), an important member of the fluoroquinolone (FQ's) was synthesized by modifying the C-3 position in a quick and facile way, using Schotten Baumann reaction approach exhibiting highly efficient yields and short reaction times. Their in-silico pharmacokinetic and toxicity studies were determined by SwissADME and Protox-II webserver, and found that all the compounds obeys the lipinski's rule and didn't exhibit any vital organ toxicity. The introduction of selected amines to form amide analogs (G-D01-G-D07) was assured by their spectroscopic characterization, structural stability studies by DFT parameters and Microbiological assay evaluates these synthesized analogs as potent antibacterial and antifungal agents against studied species. At the B3LYP/6–311 G level of theory, the molecular structures, reactivity, and electronic characteristics of candidate compounds exhibiting the most promising antibacterial actions were examined, and their quantum mechanical parameters were calculated. The energy gaps of all the synthesized compounds were found in ranges between 0.1088 and 0.1091 eV, indicating good softness, thermal and kinetic stability. This can be correlated by the activity of these analogs against Klebsiella pneumonia, and Citrobacter freundii, where synthesized derivatives G-D06 and G-D03, G-D04, and G-D07 exhibit activities more than the parent drug. The binding affinity of complexes revealed by docking was found in the range between -14.31 and -16.20 kcal/ mol, which indicates their high antibacterial potential against one of the major targets Klebsiella pneumoniae cytidine deaminase CDA protein by using AutoDock Vina and MD simulations by GROMACS, confirming them as potential antibacterial agents.