Design, synthesis and in-vitro evaluation of thiazeto [2, 3-α] quinolones as potential bioactive molecules

Kumar, Lokesh (2013) Design, synthesis and in-vitro evaluation of thiazeto [2, 3-α] quinolones as potential bioactive molecules. Masters thesis, Memorial University of Newfoundland.

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Abstract

The varied nature of biological profiles of the quinolone scaffold has attracted researcher's interests in exploring novel quinolone-based compounds. Novel quinolone derivatives are designed to overcome unwanted effects such as bacterial resistance, toxicities and side effects of existing molecules. Based on understanding of mechanism of action of quinolones, while their side effects, profile, bacterial resistance and efficacy may be altered. -- Among the newly synthesized biologically active polycyclic quinolones, the sulfur containing polycyclic quinolone nuclei such as thiazolo-, thiazeto- and thieno-derivatives are of biological interest. While there are numerous research reports available on various polycyclic quinolones, for instance 4-oxo-thiazolo [3,2-α] quinoline-3- carboxylic acid derivatives, 4-oxo-thieno [3,2-α] quinoline-3-carboxylic acid derivatives etc., there are very few studies reported for the 4-oxo-thiazeto [3,2-α] quinolines. The work presented in this thesis was performed in order to discover novel 4-oxo-thiazeto [3,2-α] quinolone derivatives with potential antibacterial activity, focusing on activity against resistant bacterial strains. This work traverses from design and synthesis of a series of 4-oxo-thiazeto [3,2-α] quinoline derivatives to their in vitro evaluation for microbiological activity, and finally ends with docking studies. Unfortunately, the antibacterial activity of the synthesized compounds was insignificant. Thus, in order to comprehend the mechanism behind the insignificant antibacterial activity, docking studies were performed on the DNA gyrase enzyme for a certain compounds. -- The results obtained from docking studies showed that the synthesized 4-oxo-thiazeto [3,2-α] quinolone derivatives could interact with the DNA gyrase enzyme, forming reversible binding interaction with the various domains of this enzyme, while other reported active antibacterial compounds from this class bind irreversibly with the ATP binding site.

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