DRUG DISCOVERY docx

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 orders@intechopen.com 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 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 ContentsVI 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. 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 of drugs. During the consumption of drugs with fruits or vegetables the ADME properties of drug (Absorption, Distribution, Metabolism and Excretion) can be modified by drug-phytochemical interaction. As a result of this interaction can be increased or decreased plasma con‐ centrations of a drug which can lead to the presence of adverse events or treatment failure. Drug Discovery2 [...]... modulation of drug- metabolizing enzymes and drug transporters lead‐ ing to potential important nutrient -drug interactions Data from: [26,52,53,55, 82, 111, 112] Table 1 Commonly Consumed Fruits 7 8 Drug Discovery Data from: [26,105,114,126, 151] Table 2 Commonly Consumed Vegetables Table 3 Fruit -Drug Interactions Fruit/Vegetable -Drug Interactions: Effects on Drug Metabolizing Enzymes and Drug Transporters... action or more toxicity) Drug- drug interactions are widely recog‐ nized and evaluated as part of the drug- approval process, whether pharmaceutical, pharmacokinetic, or pharmacodynamic in nature Equal attention must be paid to food -drug interactions (Figure 2) Figure 2 Bioassay models for studying drug- phytochemical interaction 3 4 Drug Discovery There are four types of accepted drug- food interactions... more than 50% of clinical pharmaceuticals, all nutrientdrug interactions should be considered clinically relevant, in which case all clinical studies of drugs should include a food -drug interaction screening [43] Fruit/Vegetable -Drug Interactions: Effects on Drug Metabolizing Enzymes and Drug Transporters http://dx.doi.org/10.5772/48283 5 Nutrient -drug interactions: examples with clinical relevance Fruits... Ther 69: 14-23 21 22 Drug Discovery [12] Schmidt LE, Dalhoff K (2002) Food -drug interactions Drugs 62:1481-1502 [13] Chan LN (2006) Drug- Nutrient Interactions; in Shils ME, Shike M, Ross AC, Cabal‐ lero B, Cousins RJ (eds) In: Modern Nutrition in Health and Disease Lippincott Wil‐ liams & Wilkins, 1540 p [14] Muntané J (2009) Regulation of drug metabolism and transporters Curr Drug Met‐ ab 10: 932-995... of drugs in a individual, potentially altering pharmacological responses Our knowledge regarding the potential risk of nutrient -drug interactions is still limited Therefore, efforts to elucidate po‐ tential risk of food -drug interactions should be intensified in order to prevent undesired and harmful clinical consequences Fruit/Vegetable -Drug Interactions: Effects on Drug Metabolizing Enzymes and Drug. .. have directly and indirect‐ ly shown that dietary polyphenols can modulate phase II metabolism [161] In addition, 17 18 Drug Discovery polyphenols have been shown to interact with ABC drug transporters involved in drug re‐ sistance and drug absorption, distribution and excretion [32] 6 Drug- food interaction in specific diets with high content of fruits and vegetables Weight-reduction diets, vegetarian... and Isothiocyanates: Potential for Pharmacokinetic Diet Drug Interactions Biopharm Drug Dispos 30: 335-344 [27] Huang SM Hall SD, Watkins P, Love LA, Serabjit-Singh C, Betz JM, Hoffman FA, Honig P, Coates PM, Bull J, Chen ST, Kearms GL, Murray MD (2004) Drug interac‐ Fruit/Vegetable -Drug Interactions: Effects on Drug Metabolizing Enzymes and Drug Transporters http://dx.doi.org/10.5772/48283 tions with... or modulation of renal and/or enterohepatic elimina‐ tion [13] Drug metabolizing enzymes and drug transporters play important roles in modulating drug absorption, distribution, metabolism, and elimination Acting alone or in concert with each other, they can affect the pharmacokinetics and pharmacodynamics of a drug The interplay between drug metabolizing enzymes and transporters is one of the confounding... recently shown to contribute to potential complex drug interactions [14] 3 Food and drug transporters The oral administration of drugs to patients is convenient, practical, and preferred for many reasons Oral administration of drugs, however, may lead to limited and variable oral bioa‐ vailability because of absorption across the intestinal barrier [15,16] Drug absorption across the gastrointestinal tract... isoform responsible for metabolizing an administered medicinal drug, subsequently leading to an unusually slow or fast clearance of said drug [38,39] Inhibition of drug metabolism will result in a con‐ centration elevation in tissues, leading to various adverse reactions, particularly for drugs with a low therapeutic index Often, influence on drug metabolism by compounds that occur in the environment, . nutrient- drug interactions should be considered clinically relevant, in which case all clinical studies of drugs should include a food -drug interaction screening [43]. Drug Discovery6 5. Nutrient -drug. 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. 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,