Abstract

DESIGN, IN-SILICO AND ADMET STUDIES OF TRIAZOLE BEARING QUINOLONE MOLECULAR HYBRIDS AS ANTIMICROBIAL AGENTS

Rajan Chauhan*, Purshotam and Pratibha Yadav

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Abstract

Antimicrobial resistance is a global public health problem that threaten our ability to treat bacterial infections effectively. Micro-organisms that are treated with anti-microbial drugs increase their fitness against these drugs by acquiring and expressing resistance genes and spread these genes to other microorganisms through Darwinian selection. In order to have a compound that is effective against these microorganisms, we have designed a new series of compounds that are hybrids of two different pharmacophores which are previously known to be effective against these microorganisms. The new hybrids will be having synergistic effect and resistance development will be slow. The designed compounds were compared with the reference drug ciprofloxacin. Eighteen different hybrids were made out of which 3 compounds shows good binding affinity with DNA gyrase (PDB ID: 1AJ6). The compound QT12 was having highest affinity towards DNA gyrase (-7.1 kcal/mol) which was higher than the affinity of reference drug ciprofloxacin (-6.7 kcal/mol). The compound QT5 and QT6 were having affinity of -7.0 kcal/mol which was also higher than the reference drug. Further the ADMET studies of the compound QT5, QT6 and QT12 were also done using computational methods.

Keywords: Antimicrobial resistance, quinolone, triazole, antibacterial.