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Drug Discovery DRUG DISCOVERY Edited by Hany A. El-Shemy Drug Discovery http://dx.doi.org/10.5772/3388 Edited by Hany A. El-Shemy Contributors Melanie A. Jordan, Lourdes Rodriguez-Fragoso, Irina Piatkov, Elizabeth Hong-Geller, Sonia Lobo-Planey, Pawel Kafarski, Gluza Karolina, Malemud, Jolanta Natalia Latosińska, Magdalena Latosińska, Terry Smith, Luis Jesús Villarreal- Gómez, Irma E. Soria-Mercado, Ana Leticia Iglesias, Graciela Lizeth Perez-Gonzalez, Carsten Wrenger, Eva Liebau, Taosheng Chen, Asli Nur Goktug, Sergio C. Chai, Xin Liang, Jimmy Cui, Jonathan Low, Henning Ulrich, Claudiana Lameu, Gabriel Magoma, Samuel Constant, Christophe Mas, Song Huang, Ludovic Wiszniewski Published by InTech Janeza Trdine 9, 51000 Rijeka, Croatia Copyright © 2013 InTech All chapters are Open Access distributed under the Creative Commons Attribution 3.0 license, which allows users to download, copy and build upon published articles even for commercial purposes, as long as the author and publisher are properly credited, which ensures maximum dissemination and a wider impact of our publications. After this work has been published by InTech, authors have the right to republish it, in whole or part, in any publication of which they are the author, and to make other personal use of the work. Any republication, referencing or personal use of the work must explicitly identify the original source. Notice Statements and opinions expressed in the chapters are these of the individual contributors and not necessarily those of the editors or publisher. No responsibility is accepted for the accuracy of information contained in the published chapters. The publisher assumes no responsibility for any damage or injury to persons or property arising out of the use of any materials, instructions, methods or ideas contained in the book. Publishing Process Manager Ana Pantar Technical Editor InTech DTP team Cover InTech Design team First published January, 2013 Printed in Croatia A free online edition of this book is available at www.intechopen.com Additional hard copies can be obtained from [email protected] Drug Discovery, Edited by Hany A. El-Shemy p. cm. ISBN 978-953-51-0906-8 free online editions of InTech Books and Journals can be found at www.intechopen.com Contents Preface VII Chapter 1 Fruit/Vegetable-Drug Interactions: Effects on Drug Metabolizing Enzymes and Drug Transporters 1 Lourdes Rodríguez-Fragoso and Jorge Reyes-Esparza Chapter 2 Anticancer Drug Discovery — From Serendipity to Rational Design 35 Jolanta Natalia Latosińska and Magdalena Latosińska Chapter 3 Drug Interactions, Pharmacogenomics and Cardiovascular Complication 75 Irina Piatkov, Trudi Jones and Mark McLean Chapter 4 Interactions with Drugs and Dietary Supplements Used For Weight Loss 107 Melanie A. Jordan Chapter 5 Small Molecule Screens to Identify Inhibitors of Infectious Disease 157 Elizabeth Hong-Geller and Sofiya Micheva-Viteva Chapter 6 Practical Considerations of Liquid Handling Devices in Drug Discovery 177 Sergio C. Chai, Asli N. Goktug, Jimmy Cui, Jonathan Low and Taosheng Chen Chapter 7 Data Analysis Approaches in High Throughput Screening 201 Asli N. Goktug, Sergio C. Chai and Taosheng Chen Chapter 8 Oxidative Stress in Human Infectious Diseases – Present and Current Knowledge About Its Druggability 227 Carsten Wrenger, Isolmar Schettert and Eva Liebau VI Contents Chapter 9 Discovery of Selective and Potent Inhibitors of Palmitoylation 251 Sonia Lobo Planey Chapter 10 The Antibacterial Drug Discovery 289 Jie Yanling, Liang Xin and Li Zhiyuan Chapter 11 Air, Water and Soil: Resources for Drug Discovery 309 Luis Jesús Villarreal-Gómez, Irma Esthela Soria-Mercado, Ana Leticia Iglesias and Graciela Lizeth Perez-Gonzalez Chapter 12 Transition State Analogues of Enzymatic Reaction as Potential Drugs 325 Karolina Gluza and Pawel Kafarski Chapter 13 Suppression of Pro-Inflammatory Cytokines via Targeting of STAT-Responsive Genes 373 Charles J. Malemud Chapter 14 Coupled Enzyme Activity and Thermal Shift Screening of the Maybridge Rule of 3 Fragment Library Against Trypanosoma brucei Choline Kinase; A Genetically Validated Drug Target 413 Louise L. Major, Helen Denton and Terry K. Smith Chapter 15 Colon Cancer: Current Treatments and Preclinical Models for the Discovery and Development of New Therapies 433 Samuel Constant, Song Huang, Ludovic Wiszniewski and Christophe Mas Chapter 16 Applications of Snake Venom Proline-Rich Oligopeptides (Bj- PROs) in Disease Conditions Resulting from Deficient Nitric Oxide Production 459 Claudiana Lameu and Henning Ulrich Chapter 17 Introduction to Biochemical Pharmacology and Drug Discovery 475 Gabriel Magoma Preface Natural products are a constant source of potentially active compounds for the treatment of various disorders. The Middle East and tropical regions are believed to have the richest sup‐ plies of natural products in the world. Plant derived secondary metabolites have been used by humans to treat acute infections, health disorders and chronic illness for tens of thou‐ sands of years. Only during the last 100 years have natural products been largely replaced by synthetic drugs. Estimates of 200 000 natural products in plant species have been revised upward as mass spectrometry techniques have developed. For developing countries the identification and use of endogenous medicinal plants as cures against cancers has become attractive. Books on drug discovery will play vital role in the new era of disease treatment using natural products. This book consists of 17 chapters and covers diverse topics from isolation, identification and validation and hit the drug cell interaction. I would like to thank all contributors for their excellent effort regarding the drug discovery issues and I believe this book will provide significant knowledge to students and scientists. Hany El-Shemy Faculty of Agriculture Cairo University, Egypt Chapter 1 Fruit/Vegetable-Drug Interactions: Effects on Drug Metabolizing Enzymes and Drug Transporters Lourdes Rodríguez-Fragoso and Jorge Reyes-Esparza Additional information is available at the end of the chapter http://dx.doi.org/10.5772/48283 1. Introduction Dietary habits are an important modifiable environmental factor influencing human health and disease. Epidemiologic evidence suggests that regular consumption of fruits and vege‐ tables may reduce risk of some diseases, including cancer [1]. These properties have been attributed to foods that are rich sources of numerous bioactive compounds such as phyto‐ chemicals [2]. Modifying the intake of specific foods and/or their bioactive components seems to be a prudent, noninvasive, and cost-effective strategy for preventing some diseases in people who appear to be “healthy” [3]. As will be discussed in this chapter, potential problems occur when patients taking medicines regularly also consume certain fruits or vegetables. Thousands of drugs are commercially available and a great percentage of the population takes at least one pharmacologically active agent on a regular basis. Given this magnitude of use and variability in individual nutritional status, dietary habits and food composition, there is a high potential for drug-nutrient interactions. However, there is a relatively short list of documented fruit-drug or vegetable-drug interactions, necessitating further and ex‐ tensive clinical evaluation. Healthcare providers, such as physicians, pharmacists, nurses, and dietitians, have to be aware of important food-drug interactions in order to optimize the therapeutic efficacy of prescribed and over-the-counter drugs. Here, we review some of the most widely consumed fruits and vegetables to inform healthcare providers of possible nu‐ trient-drug interactions and their potential clinical significance. There are numerous patients who encounter increased risks of adverse events associated with drug-nutrient interactions. These include elderly patients, patients with cancer and/ or © 2013 Rodríguez-Fragoso and Reyes-Esparza; licensee InTech. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. 2 Drug Discovery malnutrition, gastrointestinal tract dysfunctions, acquired immunodeficiency syndrome and chronic diseases that require the use of multiple drugs, as well as those receiving enteral nu‐ trition or transplants. Therefore, the main reason for devoting a major review to nutrient- drug interactions is the enormous importance of fruits and vegetables used for their beneficial effects as nutrients and as components in folk medicine. There are currently few studies that combine a nutrient-based and detailed pharmacological approach [4], or studies that systematically explore the risk and benefits of fruit and vegetables [5-7]. 2. Food-drug interactions A drug-nutrient interaction is defined as the result of a physical, chemical, physiological, or pathophysiological relationship between a drug and a nutrient [8,9]. An interaction is con‐ sidered significant from a clinical perspective if it alters the therapeutic response. Food-drug interactions can result in two main clinical effects: the decreased bioavailability of a drug, which predisposes to treatment failure, or an increased bioavailability, which increases the risk of adverse events and may even precipitate toxicities (See Figure 1) [4, 10,11]. Figure 1. Drug-fruit/vegetable interaction and effects on bioavailability
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