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The chemistry of 2-quinolones derivatives has received more attention in the field of both organic chemistry and medicinal chemistry. As several advances in the application of this important family of compounds seem too significant utility. In recent years, a variety of new, effective, and novel synthetic approaches (including green chemistry, catalyzed and microwave-assisted synthesis) have been discovered and developed for the designer of various 2-quinolone-based scaffolds, representing an area of increased interest to universities and industry, as well as, to explore their antibacterial activities and reduced toxicity than the existing ones. This review summarizes the results of the literature on the synthesis strategies of 2-quinolones derivatives and their reactivity, as well as their antibacterial evaluations against different bacteria strains.