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Drug action at the molecular level
414
Cell Biology
International
Reports,
Vol. 2, No. 4, 1978
DRUG ACTION AT THE MOLECULAR LEVEL Edited
by G.C.K.
The Macmillan
Roberts
Press
Ltd.,
London and Basingstoke ISBN 0 33 21494 3 - 1977 - E12.95 Attempts to extend our understanding of exactly how drugs exert their particular biological effects have involved increasing expertise in many different disciplines. This collection of papers reviews the relationship of drug action to chemical structure. The chapters in the first half of the book deal mainly with chemical and physico-chemical studies, whilst those in the second half relate more to biological and biochemical aspects. The first paper by Ganellin provides a very elegant introduction, valuable to more biologically-orientated pharmacologists, to approaches currently used to establish the molecular characteristics He then discusses and interactions of drug molecules in general. methods which may be used to "pin-point" those features which determine the biological action of the drug and indicates how such information may be valuable in altering drug structure so as deliberately to modify drug activity. Studies of drug conformations and electron interactions are discussed in the chapters by Richards and Feeney, both of whom provide experimental data from NMR spectroscopy. Richards, in addition, shows how these studies can be extended and supported by theoretical calculations. A consideration of various molecular interactions of drugs with known biological and clinical value is provided in the next few chapters. For example, the complex interaction of sulphonamides with the carbonic anhydrase isoenzymes is discussed in terms of crystal structure by Kannan et al and from a kinetic aspect by King, who emphasizes the complications inherent in a reaction involving more than a single step, perhaps with the formation of an intermediate complex. A valuable strategy for rational drug design, using the well-characterised molecule haemoglobin as a model, is proposed by Goodford. It will be interesting to read further reports of this novel approach. Studies of both cytochrome P450 and dihydrofolate reductase are rapidly becoming legion, especially for the latter enzyme. Its complexity in Lactobacillus casei, discussed by Roberts, certainly makes the prospect of attempsto work with the human enzyme in
Cell Biology International
Reports, Vol. 2, No. 4, 1978
415
future very daunting. These studies emphasize the futility and inadequacy of statements which suggest that all is known about the mechanism of action of, for example, met=rexate in cancer chemotherapy, by stating that "it is an inhibitor of dihydrofolate reductase". The later chapters in this book consider specific receptor sites for drugs which result in the overall inhibition of protein or DNA synthesis. The background information provided by Waring is again especially useful to the non-specialist and enables him to place these studies in their correct context. In general, the presentation and layout is very good and the numerous flow-diagrams and schematic representations together with the more conventional graphic and tabular illustrations, add considerably to the clarity of the text. The wish of the pharmacologist concerned with drug action at the molecular level to provide information of value in improving the drug treatment of human diseases is emphasized in this book, and whilst it is realised that there is a long way to go, from the studies described it can be appreciated that this is no mean task. However, preliminary advances seem to be being made and one hopes indeed that efforts in this direction will be rewarded ultimately.
Bridget T. Hill Department of Cellular Chemotherapy, Imperial Cancer Research Fund, London. WC2A 3PX.
Cell Biology
International
Reports,
Vol. 2, No. 4, 1978
DRUG ACTION AT THE MOLECULAR LEVEL Edited
by G.C.K.
The Macmillan
Roberts
Press
Ltd.,
London and Basingstoke ISBN 0 33 21494 3 - 1977 - E12.95 Attempts to extend our understanding of exactly how drugs exert their particular biological effects have involved increasing expertise in many different disciplines. This collection of papers reviews the relationship of drug action to chemical structure. The chapters in the first half of the book deal mainly with chemical and physico-chemical studies, whilst those in the second half relate more to biological and biochemical aspects. The first paper by Ganellin provides a very elegant introduction, valuable to more biologically-orientated pharmacologists, to approaches currently used to establish the molecular characteristics He then discusses and interactions of drug molecules in general. methods which may be used to "pin-point" those features which determine the biological action of the drug and indicates how such information may be valuable in altering drug structure so as deliberately to modify drug activity. Studies of drug conformations and electron interactions are discussed in the chapters by Richards and Feeney, both of whom provide experimental data from NMR spectroscopy. Richards, in addition, shows how these studies can be extended and supported by theoretical calculations. A consideration of various molecular interactions of drugs with known biological and clinical value is provided in the next few chapters. For example, the complex interaction of sulphonamides with the carbonic anhydrase isoenzymes is discussed in terms of crystal structure by Kannan et al and from a kinetic aspect by King, who emphasizes the complications inherent in a reaction involving more than a single step, perhaps with the formation of an intermediate complex. A valuable strategy for rational drug design, using the well-characterised molecule haemoglobin as a model, is proposed by Goodford. It will be interesting to read further reports of this novel approach. Studies of both cytochrome P450 and dihydrofolate reductase are rapidly becoming legion, especially for the latter enzyme. Its complexity in Lactobacillus casei, discussed by Roberts, certainly makes the prospect of attempsto work with the human enzyme in
Cell Biology International
Reports, Vol. 2, No. 4, 1978
415
future very daunting. These studies emphasize the futility and inadequacy of statements which suggest that all is known about the mechanism of action of, for example, met=rexate in cancer chemotherapy, by stating that "it is an inhibitor of dihydrofolate reductase". The later chapters in this book consider specific receptor sites for drugs which result in the overall inhibition of protein or DNA synthesis. The background information provided by Waring is again especially useful to the non-specialist and enables him to place these studies in their correct context. In general, the presentation and layout is very good and the numerous flow-diagrams and schematic representations together with the more conventional graphic and tabular illustrations, add considerably to the clarity of the text. The wish of the pharmacologist concerned with drug action at the molecular level to provide information of value in improving the drug treatment of human diseases is emphasized in this book, and whilst it is realised that there is a long way to go, from the studies described it can be appreciated that this is no mean task. However, preliminary advances seem to be being made and one hopes indeed that efforts in this direction will be rewarded ultimately.
Bridget T. Hill Department of Cellular Chemotherapy, Imperial Cancer Research Fund, London. WC2A 3PX.