Quinolones: Recent Structural and Clinical Developments

Quinolones are a very important family ofantibacterial agents that are widely prescribed forthe treatment of infections in humans. since their discovery in the early 1960s, the quinolonegroup of antibacterials has generated considerable clinical and scientific interest. twomajor groups of compounds have been developed from the basic molecule: quinolones andnaphthyridones. the 4-pyridone-3-carboxylic acid associated with a 5, 6-fused aromatic ringis the common chemical feature of bactericidal quinolones. in the resulting bicyclic ring, the1-, 5-, 6-, 7-, and 8-positions are the major targets of chemical variation. manipulations of thebasic molecule, including replacing hydrogen with fluorine at position 6, substituting a cyclicamine residue at position 7 and adding new residues at position 1 of the quinolone ring, haveled to improved breadth and potency of antibacterial activity and pharmacokinetics. one ofthemost significant developments has been the improved anti-gram-positive activity of the newercompounds, such as moxifloxacin and garenoxacin. however, some ofthese structural changeshave been found to correlate with specific adverse effects: the addition of fluorine or chlorineat position 8 being associated with photoreactivity, e.g. sparfloxacin; and the substitution ofan amine or a methyl group at position 5 having a potential role in qtc prolongation, e.g.sparfloxacin and grepafloxacin. the clinical utility of this expanding class of antimicrobialagents, and the lower propensity for the development of resistance with the newer quinoloneswill need to be continually monitored in the changing therapeutic environment. antibiotic drugchoice will remain difficult in the presence of increasing resistance, but introduction of the newquinolones has created a new and exciting era in antimicrobial chemotherapy.