DESIGN AND SYNTHESIS OF DNA GYRASE INHIBITORS AS ANTI-BACTERIAL AGENTS

Abstract

Anti-microbial resistance is a globally convoluted issue for public health care system. From the past 30 years, the researchers in the forte of drug resistance have abandoned the synthesis of novel antibiotics which indicates deprivation of treatment for various bacterial infections including Gram-negative & Gram-positive bacteria. Whirlwind spreading of the anti-microbial resistance has developed due to indiscriminate use of antibiotics. New mechanisms have led to the development of new potent antibiotics with broad spectrum anti-microbial activity for Gram positive and Gram-negative bacterial infections. Bacterial enzyme DNA Gyrase belongs to the class of proteins known as Topoisomerases and is responsible for the negative supercoiling of the DNA strand. In this work, we focus on the development and the various mechanisms of the newer DNA Gyrase inhibitors as antimicrobial agents to treat drug resistance caused by gram negative bacteria. Here, by using the software GOLD the docking study was carried out for the designed derivatives of the compounds. The compounds showing the highest score was chosen to predict the binding of the compound to that of the structure which were then docked on the protein structure (PDB id: 1KZN). Out of the series, synthesis was carried out for the compounds UA-25 & UA-27 showing nearby docking scores to that of the standard. Activity of the compound was carried on normal as well as on the resistant strains of E.coli as a result the synthesised compound UA-25 was proved to have no biological activity on the normal as well as on the resistant strains of E.coli ATCC25922.