Book Review Medicinal Chemistry. The Role of Organic Chemistry in Drug Research. Edited by C. R. Ganellin and S. M. Robertsкод для вставкиСкачать
BOOKS An Overall Picture of Biomembranes from the Mosaic of Data Biomembranes. Physical Aspects. Edited by M . Shimitzky. VCH Verlagsgesellschaft, Weinheim/VCH Publishers, New York, 1993. 371 pp., hardcover DM 198.00, $ 135.00.ISBN 3-527-30021-X/l-56081-771-2 This book is the first volume in a series that aims to provide a structure for the many-faceted subject of biological membranes; it is concerned with the physical phenomena that result from the integrity and fluidity of lipid double layers. This is a well-chosen topic to begin the series, as it introduces the basic principles for later discussions of membrane functions. Although the present picture of lipid membrane structures is fairly clear, it is a mosaic made up of many thousands of publications. Does this book fulfill its claim to provide the picture with a structure‘? I n my view it mainly does; three of the chapters achieve this especially well, and these will be described first. In Chapter 4 on “Fluidity, Dynamics, Order”, B. Wieb van der Meer defines in a brief and simple way six types of dynamic processes in lipid membranes. then treats these in a textbook style, comparing and evaluating their importance. Molecular alignment, domain formation, and asymmetry in membranes are thoroughly discussed, as also are basic concepts. methods, and current problems. The bibliography to this chapter is systematically arranged and includes full titles. enabling the reader to quickly find material on topics of particular interest. Chapter 7 on the electrical properties of membranes (L. M. Loew) is much shorter, but this too strikes me as perfect in its way. Here again one finds an easily readable text, with illustrations that are precisely in harmony with it, and the I This section contains hook reviews and a list of nen hook:, received by theeditor. Book reviews are written by invitation from the editor. Suggestions for hooks to be reviewed and for book reviewers are welcome. Publishers should send brochures or (better) books to Dr. Ralf Baumann. Redaktion Angewandte Chemie. Postfach 101 161. D-69451 Weinheini. Federdl Republic of Germany. The editor reserves the right of selecting which books will bc rtbiewed. Uninvited books not chosen for revim will not hc returncd. titles of the most important publications are given. Also very pleasing is Chapter 6, in which Y I. Henis gives a detailed description, with up-to-date illustrations, of the interesting method of “fluorescence photobleaching recovery”. On the other hand, the remaining four chapters are competently written surveys of particular topic areas, rather than attempts at providing a structure. In Chapter 1 D. Marsh summarizes the thermodynamic equations from the more extensive treatment in his book Phospholipid Biluyers, but a clear physical model fails to emerge from the illustrations or from the qualitative descriptions of the forces that are at work. Chapter 2. by D . Chapman, is concerned with phase transformations in lamellar, hexagonal, and cubic phases. In my view this does not really fit into the subject of biomembranes. despite the inclusion of a section entitled “Biological Relevance” which introduces comparisons with cell partitioning, domain formation, etc. The same comment applies to the topic of micelles in Chapter 3 by D. Lichtenberg. since to my knowledge micelles in the usual sense do not occur in biological systems. In contrast liposomes are not treated in sufficient detail. There are no electron micrographs of these. nor is there anything on fusion models or undulations. Most of the figures are more likely to mislead than to elucidate the text (examples: Figs. 8 and 9 show micelles that are not curved, which is very untypical; Fig. 4 shows turbidity occurring as a result of micelle formation, despite the fact that micellar solutions are nearly always quite clear; Fig. 2 shows molecular models that are cone-shaped, even though there are no examples of these). That leaves only Chapter 5 on lipid-protein interactions, by A. H. Parola, which is by far the longest in the book. I feel that the content of this chapter is well summarized by the author’s comment on page 221 that “...work on membrane protein purification and reconstitution leaves very limited evidence of specific lipid requirements for membrane protein reactivation ...”. The listing of the many proteins whose interactions with liposomes have been investigated makes boring reading for the nonspecialist, and the discussion of the results yields few surprises. On the other hand, a novel idea that could be important is the model of malignant plasma membranes with intercalated domains of electroneutral lipids (also containing DNA?-this point is not made clear). The comprehensive survey of protein- lipid interactions is, of course, of central interest to the specialist reader. The book is undoubtedly an important addition to the literature for the reader envisaged in the preface, who is engaged in research in this field. He or she will find here comprehensive information on membrane fluidity, membrane proteins, and electrical properties. However, this thorough coverage extends only up to 1988; beyond that it becomes thin. For the students also envisaged as potential users, I recommend Chapters 4, 6, and 7 as readable introductions; they will also find Chapter 5 useful, although much of it can be skipped over. With regard to the introductory Chapters 1 -3, the student would be better served by other books, such as Phospholipid Bi1qvr.c. by G . Cevc and D. Marsh, Menibrune Mimetic Cliertiistry, by J. H. Fendler. and Iii~ermolcculur and Surfuce Forces. by J. N. Israelachvili. It is not until Chapter4 when the focus turns to biological aspects that the book begins to fulfill its special objective. One must therefore hope for the best in the volumes that are to follow. Jiirgetl-H. FUhi‘ll(p Institut fur Organische Chemie der Freien Universitiit Berlin (FRG) Medicinal Chemistry. The Role of Organic Chemistry in Drug Research. Edited by C. R. Ganellin and S. M . Roberts. Academic Press, London, 1993. 302 pp., hardcover E 29.00.ISBN 0-12-274120-X Eight years after the publication of the first edition of this book, this new edition has appeared. It consists of 14 chapters with 17 authors, offering the reader an excellent survey of the pharmacological aspects and the synthesis, development, and medical importance of new pharmaceutical products. The descriptions of pharmacologically active compounds and their meth- BOOKS ods of preparation are illustrated throughout by structural formula diagrams. Seven of the chapters are revised and updated treatments of topics that were included in the first edition, and these appear at the beginning and end of the new version, as follows: Chapter 1. “Introduction to Receptors and the Action of Drugs”; Chapter 2. “Structure and Catalytic Properties of Enzymes”; Chapter 3. “Receptor Pharmacology”; Chapter 10, “Beta Blockers”: Chapter 11, “Salbutamol: A Selective P2-Stimulant Bronchodilator”; Chapter 12, “Discovery of Cimetidine, Ranitidine and other H,-Receptor Histamine Antagonists”; Chapter 14. “Clavulanic Acid and Related Compounds: Inhibitors of P-Lactamase Enzymes”. The new chapters that have been added are: Chapter 4, “Drug Access and Prodrugs”; Chapter 5. “QSAR and the Role of Computers in Drug Design”; Chapter 6. “The Current Status and Future Impact of Molecular Biology in Drug Discovery”; Chapter 7, “General Approaches to Discovering New Drugs: A Historical Perspective”; Chapter 8, “Discovery and Development of Cromakalim and Related Potassium Channel Activators”; Chapter 9, “Angiotensin-Converting Enzyme (ACE) Inhibitors and the Design of Cilanapril”; Chapter 13, “Fluconazol. an Orally Active Antifungal Agent”. Following the introduction to the general principles of pharmacology in the first half of the book, the emphasis in the second half is on the practical importance of pharmaceutical compounds in areas where there is likely to be impressive progress in the age of our modern industrial society. Chapter 8 describes a new therapeutic principle for the treatment of cardiac and circulatory disorders and bronchial asthma, which is becoming increasingly important with the discovery of the mechanism whereby cromakalini acts as a potassium channel activator. Chapter 9 is concerned with ACE inhibitors, which are now the most favored agents for the treatment of hypertension and cardiac degeneration. The development of ACE inhibitors such as captopril, enalapril, and cilazapril is described, together with their biological properties. Chapter 10 discusses the chemistry, pharmacology. and clinical effects of beta blockers, which competitively and reversibly inhibit the positive inotropic and chronotropic effects of catecholamines on the heart (by blocking the P, receptors), and also inhibit bronchospasmolysis by blocking the p, receptors. Chapter 11 is concerned with salbutamol and analogous compounds derived from adrenalin and isoprenalin, which are used in the treatment of bronchial asthma. Chapter 12 is devoted to cimetidine and ranitidine. two compounds that rank as milestones in the development of H,-receptor histamine antagonists and are used in the treatment of gastritis and ulcers; their preparation is described in detail and structureeactivity relationships are discussed. Chapters 13 and 14 are concerned with antiinfectives, in particular with the widely used orally active antifungal agent fluconazol and with clavulanic acid which is used as an inhibitor of p-lactamase enzymes. A combination of clavulanic acid with amoxicillin has proved successful as a further development in the penicillins field. This altogether excellent book, an enlarged revision of the edition published in 1985, is a valuable addition to other recently published books on medicinal chemistry (R. B. Silverman, Tj7e Organic Clzetnistry qf’ Drug Design and Drug Action; B. Testa, W. Fuhrer, E. Kyburz, and R. Giger, Perspectives it1 Medicinal Chrmistrj~;both published in 1992). Medicinal Chernistrj. contains many valuable articles which help the reader to understand important concepts of pharmacology and molecular biology, and describe new developments in pharmacological agents. Gunter Schrnidt Bayer AG Wuppertal (FRG) 2D NMR. Density Matrix and Product Operator Treatment. By G. D. Muteescu and A . Vuleriu. PTR Prentice Hall, Englewood Cliffs, 1993. 200 pp., hardcover $ 50.00.--ISBN 0-1 3-013368-X This book aims to provide the reader with a detailed guide to analyzing multiplepulse N M R experiments, using the density matrix and product operator approaches. The text is deliberately and unashamedly didactic in its approach, and the calculations are set out step-by-step without leaving out any intermediate results. In addition, the manipulations by which a result is simplified and interpreted are also set out in some detail. The first section of the book is devoted to examples of the use of the density matrix approach, the first such example being an analysis of the HETCOR experiment whereby one observes 13C and obtains a two-dimensional I3C- ‘H shift correlation spectrum. The authors introduce the concept of the density matrix. explaining how to set up the equilibrium conditions, the effect of pulses, how to calculate evolution. and finally how to calculate observables. Each of these ideas is introduced as it is needed in deducing the effect of the pulse sequence. and so there is a natural flow to the discussion. with the concepts appearing in context. Having completed the analysis. the authors then compare this with an attempt at a vector analysis of the sequence, showing that the vector method is at best cumbersome. and at its worst extremely confusing. The reader is left with the impression that multiplying matrices together is preferable to trying to understand the apparently random rules that govern these vectors. The main criticism of this opening section is that it rather fudges the important issue of the connection between the terms one sees at the end of a calculation and the appearance of a two-dimensional spectrum. The authors do not make a clear distinction between terms which simply affect the amplitude or phase of a peak and those which contain the information about the frequencies present in the F , spectrum. Further, the connection between the form of these terms and the phase (or even sign) of the peaks in the spectrum is not well described. The density matrix section goes on to cover the INADEQUATE and COSY procedures. As before. the issues of phase and lineshapes are somewhat lost, and the difference between the phase properties of the cross and diagonal peaks in COSY spectra receives scant attention. The section closes with a discussion of “phase cycling” in the COSY experiment; in fact the topic covered is frequency discrimination. which is rather a different matter. The second section of the book goes on to introduce the product operator formalism, again using the approach of showing how a calculation is done and highlighting the rules by which these operators are manipulated. Some time is spend on establishing the relationship between the operators, their matrix representations, and observable signals; this is a welcome discussion. Once again HETCOR is used as the first example but, incredibly, this is the only two-dimensional experiment analyzed using product operators. The remainder of the examples are all one-dimensional experiments, such as DEPT; in these cases the analysis is extended to include magnetic equivalence. It is very unfortunate that the authors did not include COSY and double-quantum-filtered COSY as examples, as these both provide excellent vehicles for explaining the usefulness and properties of product operators. Generally speaking, this section on product operators does not read well; the overall impression is one of confusion, and a lack of structure and authority.