Chemical Education Today
Book & Media Reviews
Medicinal Chemistry—An Introduction by Gareth Thomas John Wiley & Sons: New York, 2000. 568 pp. ASIN 0471988073 (cloth). $50; ISBN 0471489352 (paper). $44
Fundamentals of Medicinal Chemistry by Gareth Thomas John Wiley & Sons: New York, 2003. 302 pp. ISBN 0470843063 (cloth). $85; ISBN 0470843071 (paper). $30 [Also available digitally as an e-book using Adobe Reader: John Wiley & Sons: New York, 2004. MAC OS 10.2 or higher, Windows. ISBN B0001WPRT6. $30] reviewed by Eugene Gooch
For years, special topics courses such as medicinal chemistry have occupied a unique place in the curriculum. Among students they stimulate interest in the discipline and are effective at recruiting majors. Faculty instructors also find intellectual stimulation in teaching something outside the usual set of courses, even when the topic is not part of their own academic training. The broad appeal of medicinal chemistry (and forensic and environmental chemistry) is indicated by a generous number of articles and lab experiments in this Journal (1–5). There is a fundamental tension between the desire to teach something unique and the desire to teach a topic thoroughly and rigorously. There is a certain appeal to the “hardcore traditionalist” in each of us to pursue the latter course. Those departments that wish to include medicinal chemistry in an ACS-certified B.S. degree might deem it an advanced course with physical chemistry as a prerequisite, and use the traditional descriptive approach found in Silverman’s text (6). However, when enrollment pressures (or textbook sales) have to be considered, many instructors adjust their attitude. There is a larger market for titles that could be termed “readers”—user-friendly texts designed to accommodate students with fewer chemistry credits on their transcript. Despite being discounted by some as “fluffy”, these texts are just as effective at stimulating interest in chemistry among undergraduates. To cover both situations, Gareth Thomas has written two texts designed for a single semester course: Medicinal Chemistry—An Introduction (which I will call “MCI”) and Fundamentals of Medicinal Chemistry (referred to as “FMC”). MCI is a remarkably lucid and cogent text—I really like this book! It strikes a middle ground between “readers” and books as descriptively detailed as Silverman’s. MCI assumes “a knowledge of chemistry at level one of a university life sciences degree”. In practice this means students should be comfortable (not just acquainted) with many of the mathematical applications found in general chemistry (first- and www.JCE.DivCHED.org
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second-order kinetics, equilibrium mass action expressions, buffers, Henry’s Law, Ksp) as well as enough organic chemistry to be conversant with common functional groups and reactions. A smattering of calculus, while not essential, makes the road easier when Thomas covers pharmacokinetics by injecting the occasional: “dA/dt = rate of absorption – rate of elimination.” I should not convey the impression that the book is highly mathematical. Math is used in only about 20% of the book; but where you find it, it is used at an appropriate level, with fine effect. Enzyme kinetics are covered simply and elegantly in as much detail as some standard biochemistry texts, although a complete derivation of the Michaelis–Menten equation is not provided. The essentials of using linear free energy constants to model solubility (log P) and pharmacological potency are presented concisely. The QSAR details offered on the Taft parameter and the Hansch approach are as suitable as they are succinct. If an instructor wishes to inject a little more P-chem into the course, it is an easy transition to include linear free energy relationships, consecutive first-order kinetics, and the steady-state approximation without immediately admitting to the students what you are doing. A significant number of students are pleasantly surprised later when they realize they learned some P-chem in a relatively painless manner (derivations or quantum mechanics, anyone?) Drug metabolism and prodrugs are packaged together nicely with a very smooth transition in a single chapter. Other chapters focus on sites of drug action: a polished introduction to DNA/RNA is followed by descriptive material on drugs found to (or designed to) act specifically on them— the same approach is then taken with enzymes and membranes. A brief chapter on complexes and chelating agents and another on nitric oxide provide unique diversions that show considerable thought and reflection by the author in his choice of topics. A section on viruses and antiviral agents in the DNA chapter mentions AZT, but oddly no explicit reference to AIDS is made. Finally, each chapter has about a dozen study questions, with answers provided in the back of the book. As mentioned earlier, Thomas has rewritten MCI to fit the demand for a “reader”; the result is Fundamentals of Medicinal Chemistry. Of necessity the text begins with a chapter reviewing biomolecules. It serves as an adequate review of the last few chapters in most organic texts (or replaces them if the organic instructor had chosen to skip them). It is liberally sprinkled with structures and rather clean line drawings. While introducing the basic properties of drugs and surveying the process of drug discovery, Thomas has chosen to limit his digression into historical details. This “lean and mean” approach streamlines his text relative to other titles that seem rather burdened with a conglomeration of historical trivia. The next chapter, “An Introduction to Drugs and Their Action”, contains most of the terminology used later in the book; but so many terms are introduced in boldface that it seems little more than an embellished glossary. Such
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Chemical Education Today edited by
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are the compromises that must occur to keep a text both userfriendly and brief. The answers to the study questions in FMC are rather disappointing; many of them simply refer the reader to a particular section in an earlier chapter, reinforcing a “memorize and regurgitate” study method. Another compromise is the inclusion of 12 (!) extremely short appendices, suggesting that either the publisher or reviewers insisted that certain topics not be completely neglected. Maybe I just think that MCI is so good that it’s a hard act to follow. Despite my evident bias, I must declare that FMC is a good product that delivers according to the way it was designed. The chapters on SAR/QSAR, computer-aided drug design, synthetic methods, combinatorial methods, and pharmacokinetics, while briefer, are not fundamentally different from MCI; they are endowed with the same lucid writing style described earlier. Brief sections on drug development and production, as well as computer-assisted drug design in MCI, are expanded to full chapters in FCM. The development chapter contains a summary of the different phases of clinical trials that a drug must experience prior to approval. (This parallels what other authors have done.) On the other hand, the fine and detailed coverage of receptors in MCI is relegated to 2 1/2 pages in one of the appendices. I would recommend that an instructor who is completely new to the field of medicinal chemistry purchase both texts. Build your knowledge base by reading Fundamentals of Medicinal Chemistry first, then read Medicinal Chemistry—
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An Introduction. Next, browse through MCI’s supplementary reading list of over 30 titles (if you have time for the additional reading). Only then can you decide which text to use in your class. Literature Cited 1. Stachulski, Andrew V.; Lennard, Martin S. Drug Metabolism: The Body’s Defense against Chemical Attack. J. Chem. Educ. 2000, 77, 349. 2. Balaban, Alexandru T.; Seitz, William. Relevance of Chemical Kinetics for Medicine: The Case of Nitric Oxide. J. Chem. Educ. 2003, 80, 662. 3. Agosta, William C. Medicines and Drugs from Plants. J. Chem. Educ. 1997, 74, 857. 4. Muranaka, Ken. Anticancer Activity of Estradiol Derivatives: A Quantitative Structure-Activity Relationship Approach. J. Chem. Educ. 2001, 78, 1390. 5. Prado, Maria Auxiliadôra Fontes. Determination of Lipophilicity Constants of Sulfonamide Substituents. J. Chem. Educ. 2001, 78, 533. 6. Silverman, R. B. The Organic Chemistry of Drug Design and Drug Action, 2nd ed.; Elsevier Academic Press: London, 2004.
Eugene Gooch is a professor in the Chemistry Department at Elon University, Elon, NC 27244;
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