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Abstract: The chemistry of 2-quinolones derivatives has received more attention in organic chemistry and medicinal chemistry. Moreover, several advancements in the application of this family of compounds are considered to be of great 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 designing of safe and non-toxic 2-quinolone-based scaffolds to investigate their antibacterial activities. 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.