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It has been over 30 years since the first clinically important
member of the quinolone class, nalidixic acid, was introduced into
medical practice. The modification produced in the quinolone
nucleus by introducing a fluorine at the 6-position led to the
discovery of the newer fluoroquinolones with enhanced antibacterial
activities as compared to nalidixic acid. By now a great deal of
preclinical and clinical experience has been obtained with these
agents. The intense interest in this class of antibacterial agents
by chemists, micro biologists, toxicologists, pharmacologists,
clinical pharmacologists, and clini cians in various disciplines
encouraged us to summarize the information on the history,
chemistry, mode of action and in vitro properties, kinetics and
efficacy in animals, mechanisms of resistance, toxicity, clinical
pharmacology, clinical experience, and future prospects in one
volume of the Handbook of Experimental Pharmacology. As this series
deals predominantly with "experimental" characteristics of drugs,
our volume is dedicated specifically to quinolones and emphasizes
principally their preclinical and clinical phar macological
characteristics, despite the existence of several summaries on
quinolones. The chemistry of the quinolones is described in detail.
The chapter on the mode of action of quinolones reports the
conclusive evidence that gyrase is the intracellular target of the
quinolones; however, another enzyme, topoisomerase IV, may also be
a target for quinolones, and the exact mechanisms by which
quinolones act bactericidally are far from being understood."
At a symposium in Wuppertal held on 26 September 1995, Dr.
Karl-Georg Metzger was honored, on the occasion of his retirement,
for his scientific contributions and involvement in antibacterial
drug research and develop ment within Bayer AG. In 1963 Dr. Metzger
was the first "molecular micro biologist" to join Bayer in the
field of antibacterial research. Karl-Georg Metzger studied physics
and biology at the University of Mainz from 1950 to 1953 and
continued his scientific education, with a grant from the Deutsche
Forschungsgemeinschaft, in Frankfurt on Main (1953-1956). From 1956
to 1958, under Professor Kaplan, he worked on his DNA following
treatment of PhD, studying on "Energy conduction along bacteria
with UV light and X-rays and the formation of mutations". He was
awarded his PhD in 1959. From 1958 to 1963 he was research
assistant in ra diobiology development at the Institute of Genetics
in Cologne. During the following years he became fascinated by the
emerging fields of molecular biology and gene technology. He worked
together with the molecular gen eticists W. Harms and M. Delbriick,
who built up one of the most renowned institutes in the world, in
Cologne. ''An incredibly interesting time:' Dr. Metzger remembers,
in which he got to know a whole series of Nobel prize winners from
Niels Bohr to Watson and Crick and Joshua Lederberg, the first to
recombine genotypes of bacteria.
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