Design, Synthesis, Molecular Docking, and Antibacterial Evaluation of Some Novel Flouroquinolone Derivatives as Potent Antibacterial Agent

Abstract

Objective. Quinolone moiety is an important class of nitrogen containing heterocycles widely used as key building blocks for medicinal agents. It exhibits a wide spectrum of pharmacophores and has bactericidal, antiviral, antimalarial, and anticancer activities. In view of the reported antimicrobial activity of various fluoroquinolones, the importance of the C-7 substituents is that they exhibit potent antimicrobial activities. Our objective was to synthesize newer quinolone analogues with increasing bulk at C-7 position of the main 6-fluoroquinolone scaffold to produce the target compounds which have potent antimicrobial activity. Methods. A novel series of 1-ethyl-6-fluoro-4-oxo-7-{4-[2-(4-substituted phenyl)-2-(substituted)-ethyl]-1-piperazinyl}-1,4-dihydroquinoline-3-carboxylic acid derivatives were synthesized. To understand the interaction of binding sites with bacterial protein receptor, the docking study was performed using topoisomerase II DNA gyrase enzymes (PDB ID: 2XCT) by Schrodinger's Maestro program. In vitro antibacterial activity of the synthesized compounds was studied and the MIC value was calculated by the broth dilution method. Results. Among all the synthesized compounds, some compounds showed potent antimicrobial activity. The compound 8g exhibited good antibacterial activity. Conclusion. This investigation identified the potent antibacterial agents against certain infections.

Optimization Rules for SARS-CoV-2 Mpro Antivirals: Ensemble Docking and Exploration of the Coronavirus Protease Active Site

“…Some docking studies have been performed on already available drug compounds to rank their potential for development as antiviral agents [20,21]. Studies using molecular docking have been utilized to analyze binding interactions of antiviral compounds targeting; the HIV protease [22,23], topoisomerase II DNA gyrase enzymes [24,25], and anti-cancer compounds which target histone deacetylases [26][27][28] and a range of other diseases can assist in the optimization of molecular interactions for drug design. Studies performed to explore the broad substrate binding preferences that SARS-CoV-2 M pro has would therefore significantly assist in the optimization of any lead drug compounds that are being pursued.…”

A Novel In Silico Benchmarked Pipeline Capable of Complete Protein Analysis: A Possible Tool for Potential Drug Discovery

“…The required protein models were obtained from the Protein Data Bank (RCSB). After the docking process, the interacting amino acids of the proteins in each protein–protein interaction were analyzed using Maestro BioLuminate 2.8 software and LigPlot+ [ 44 , 45 ].…”

Fluoroquinolones’ Biological Activities against Laboratory Microbes and Cancer Cell Lines

“…As reported, norfloxacin was used as a positive control in the pipeline publications, including norfloxacin derivatives synthesis. Norfloxacin MIC against Gram-positive is presented in Table 3 [ 1 , 23 , 24 , 26 , 28 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 , 61 , 62 , 63 , 64 , 65 , 66 , 67 , 68 , 69 , 70 , 71 ]. In brief, norfloxacin inhibitory activity against a panel of Gram-positive bacteria regardless of the strain varied relatively.…”