Conventional-Microwave Mediated Synthesis and In Vitro Antimicrobial Activity of Novel Carbazole-Efflux Pump Inhibitor Hybrid Antibacterials

Ghazala Yaqub,Zubi Sadiq,Almas Hamid,Amber Fatima,Zainab Ijaz

doi:10.1155/2017/7243279

Abstract

Work presented herein is the first report of two dual-action hybrids synthesized by covalent linkage of carbazole based novel antibacterial compounds with efflux pump inhibitors, that is, indole acetic acid/gallic acid. In this paper, novel antibacterial compounds 2 and 3 were prepared first and then these were covalently linked with efflux pump inhibitors, that is, indole acetic acid/gallic acid leading to the successful formation of two dual-action hybrids 4 and 5. Prepared antibacterials and hybrids were evaluated for their bacteria cell killing capability against Escherichia coli, Staphylococcus aureus, Pasteurella multocida, and Bacillus subtilis. Both antibacterial compounds 2 and 3 were found effective against all tested bacterial strains at different concentrations. But when these compounds were linked with efflux pump inhibitors, they showed dramatic enhancement in their bacterial cell killing potential and minimum inhibitory concentration of all hybrids ranging from 7.250 μg/mL to 0.05 μg/mL. These prepared hybrid drugs will be promising and effective new agents in the category of dual-action antibiotics.

Highlights

Since the past 60 years, antibiotics have been considered critical for the treatment of infectious diseases caused by bacteria and other microbes [1]
Some novel potential antibiotics were synthesized first and these antibiotics were covalently linked with efflux pump inhibitor, that is, indole acetic acid to prepare dual-action hybrids, that is, 4 and 5 (Scheme 1)
Both antibacterial compounds and dualaction hybrids were prepared via microwave mediated synthesis along with conventional synthetic routes

Summary

Introduction

Since the past 60 years, antibiotics have been considered critical for the treatment of infectious diseases caused by bacteria and other microbes [1]. The problem of antibiotic resistance in bacteria emerged due to discriminate use of existing antibiotics by human beings This led to the development of several modifications in pathogenic bacteria and other disease causing microbes to resist antibiotics and other antimicrobial drugs. The most effective mechanism by which a large number of the bacteria resist antibiotics is the physical removal of the antibiotic from the cell using efflux pumps of bacteria. These multidrug efflux pumps in bacteria provide a universal mechanism by which bacteria resist many antibiotics [4].

Methods

Results

Conclusion