© 2003 The British Society for Antimicrobial Chemotherapy Development of the quinolones

Since their discovery in the early 1960s, the quinolone group of antibacterials has generated considerable clinical and scientific interest. Nalidixic acid, the first quinolone to be developed, was obtained as an impurity during the manufacture of quinine. Since this time, many deriva-tives have been synthesized and evaluated for their antibacterial potency. Two major groups of compounds have been developed from the basic molecule: quinolones and naphthyridones. Manipulations of the basic molecule, including replacing hydrogen with fluorine at position 6, substituting a diamine residue at position 7 and adding new residues at position 1 of the quino-lone ring, have led to enhanced antibacterial efficacy. In general these compounds are well toler-ated. However, some of these structural changes have been found to correlate with specific adverse events: the addition of fluorine or chlorine at position 8 being associated with photo-reactivity, e.g. Bay y 3118 and sparfloxacin; and the substitution of an amine or a methyl group at position 5 having a potential role in QTc prolongation, e.g. sparfloxacin and grepafloxacin. Pro-gressive modifications in molecular configuration have resulted in improved breadth and potency of in vitro activity and pharmacokinetics. One of the most significant developments has been the improved anti-Gram-positive activity of the newer compounds, such as moxifloxaci