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

Oussama Moussaoui,Abdeslem Ben Tama,Said Chakroune,Outi M H Salo-Ahen,Riham Sghyar,El Mestafa El Hadrami,Rajendra Bhadane,Youssef Kandri Rodi,Soukaina El Amrani

doi:10.3390/scipharm88040057

Oussama Moussaoui, Abdeslem Ben Tama + Show 7 more

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https://doi.org/10.3390/scipharm88040057

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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.

Highlights

Antibacterial compounds have been protecting human society from serious bacterial infections for almost 70 years
The results suggest that these 2-quinolone derivatives could serve as potential starting points for the development of novel antibacterial agents
The DNA gyrase subunit A (GyrA) and subunit B (GyrB) sequences of E. coli, P. aeruginosa, S. aureus and B. subtilis were retrieved from the UniProt database [34] and aligned using the Clustal

Summary

Introduction

Antibacterial compounds have been protecting human society from serious bacterial infections for almost 70 years. Increased antibacterial resistance poses a big threat for the effectiveness of existing antibacterial agents. There is an urgent need for the development of novel and improved antibacterial compounds [1]. Quinolones represent one of the oldest classes of synthetic antibacterial compounds with a broad spectrum of activity. They were developed from the narrow-spectrum prototype of quinolones, nalidixic acid, which was reported in 1962 [2]. In the late-1970s and 1980s, the development of fluoroquinolones considerably improved the antibacterial activity of this class

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