Polycyclic quinolones: design, synthesis, preliminary in vitro and in silico studies

Shukla, Ranjeet Rahul (2012) Polycyclic quinolones: design, synthesis, preliminary in vitro and in silico studies. Masters thesis, Memorial University of Newfoundland.

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Abstract

4 (1H)-Quinolone is an important phamacophore found in a variety of biologically active molecules including clinically used antimalarial, antibacterial, anti-inflammatory, anticancer and antiviral agents. The diverse biological profiles of quinolone derivatives have attracted researchers interested in exploring novel quinolone-based compounds that may overcome the unwanted effects of life-saving drugs while presenting new mechanisms of action and high efficacy. -- Among the quinolone derivatives, 4 (1H)-quinolone-3carboxylic acid derivatives have displayed an excellent antibacterial profile. This includes high efficacy, broad spectrum of activity, high tolerability, and effectiveness against bacterial strains resistant to available antibiotics. The work presented in this thesis was performed in order to discover novel polycyclic quinolones with potential antibacterial activity, focussing on activity against resistant bacterial strains. This work involves the design and synthesis of various fused quinolones and their in vitro microbiological activity. In order to understand the mechanism behind the loss of activity, in silico molecular docking was carried out on the DNA gyrase enzyme. -- The results obtained in this study showed that the synthesized quinolone derivatives have good binding affinities to DNA gyrase. However, these derivatives were not able to form stable bonds with the enzyme, which may account for the lack of bioactivity exhibited by these derivatives.

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