Methods of Synthesis and Bioactivity of 3-Carboxy-quinolin-4(1H)-ones

The 3-carboxy-quinolin-4(1H)-ones constitute an important group of antimicrobial agents widely used in treatment of several diseases. The nalidixic acid, the first quinolone derivative developed as antibacterial agent in the early 1960s, was used as prototype to this group improvement. However, these compounds were neglected until the development of fluoroquinolones. The research associated to these antibiotics has been developed since ciprofloxacin was employed in the late 1980s, and from that period on it has been object of study. The versatility of 3-carboxy -quinolin-4(1H)-ones is associated to their wide range of biological activities reported in the literature, such as: antibacterial, antiviral, antiprotozoal, antifungal, and antitumoral. This review gives a highlight to the main synthetic methodologies for the synthesis of these heterocycles: Gould-Jacobs, Grohe-Heitzer, Baylis-Hillman, reactions employing transition metals and solid-phase reactions. Additionally, examples of the influence of chiral substituents on antibacterial activity are presented.