Novel Amino Acid Derivatives of Quinolines as Potential Antibacterial and Fluorophore Agents

Abstract

A new series of amino acid derivatives of quinolines was synthesized through the hydrolysis of amino acid methyl esters of quinoline carboxamides with alkali hydroxide. The compounds were purified on silica gel by column chromatography and further characterized by TLC, NMR and ESI-TOF mass spectrometry. All compounds were screened for in vitro antimicrobial activity against different bacterial strains using the microdilution method. Most of the synthesized amino acid-quinolines show more potent or equipotent inhibitory action against the tested bacteria than their correspond esters. In addition, many of them exhibit fluorescent properties and could possibly be utilized as fluorophores. Molecular docking and simulation studies of the compounds at putative bacterial target enzymes suggest that the antimicrobial potency of these synthesized analogues could be due to enzyme inhibition via their favorable binding at the fluoroquinolone binding site at the GyrA subunit of DNA gyrase and/or the ParC subunit of topoisomerase-IV.

Design, Synthesis, Molecular Modeling, Biological Activity, and Mechanism of Action of Novel Amino Acid Derivatives of Norfloxacin

“…Increasing antibiotic resistance has created an urgent need for novel antibacterial agents and strategies. Both Gram-positive and Gram-negative bacteria, as well as mycobacteria, contribute to this problem . Bacterial strains that accumulate multiple resistances are of particular concern; e.g.…”

“…Both Gram-positive and Gram-negative bacteria, as well as mycobacteria, contribute to this problem. 1 Bacterial strains that accumulate multiple resistances are of particular concern; e.g., methicillinresistant Staphylococcus aureus (MRSA) poses a constant threat of severe nosocomial infections. Several cases of pan-resistant Gram-negative bacteria have resulted in untreatable infections, most prominently Pseudomonas aeruginosa, Klebsiella pneumoniae, and Acinetobacter baumannii.…”

“…tively. In addition to anticipated aromatic protons,1 HNMR spectra of 7a−i also showed triplet (in the case of glycine amino acid) or doublet (in the case of alanine, cysteine, and asparagine amino acids) signals at δ 10.44−10.16 ppm assigned to amidic CONH and broad singlet signals at δ 12.55−10.35 ppm assigned to the COOH group. Compounds 7a−d showed doublet signals at δ 4.50−4.04 ppm assigned to the NHCH 2 CO group, which appeared as δ 4.46 ppm multiplet for compounds 7e−f, which also showed a doublet peak at δ 1.36−1.26 ppm assigned to the COCHCH 3 group.…”

Design, Synthesis, in vitro and in silico Characterization of 2‐Quinolone‐L‐alaninate‐1,2,3‐triazoles as Antimicrobial Agents

“…In this context, the antimicrobial importance of polyheterocyclic systems such as 2‐quinolones is well established. The 2‐quinolone moiety is among the most widely used synthetic scaffolds that researchers have used for successful design of new antimicrobial agents [11–25] . One useful strategy has been to create hybrid molecules [26] using two different pharmacophoric moieties with antimicrobial effects.…”

“…The 2‐quinolone moiety is among the most widely used synthetic scaffolds that researchers have used for successful design of new antimicrobial agents. [ 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 ] One useful strategy has been to create hybrid molecules [26] using two different pharmacophoric moieties with antimicrobial effects. 2‐Quinolones could be combined with, for example, the privileged scaffolds of 1,2,3‐ or 1,2,4‐triazoles[ 27 , 28 , 29 ] that have both been widely applied not only in medicinal chemistry[ 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 ] but also in material science.…”