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- Herausgeber: Wiley-VCH
- Kategorie: Wissenschaft und neue Technologien
- Sprache: Englisch
Natural compounds, which have evolved their function over millions of years, are often more efficient than man-made compounds if a specific biological activity is needed, e.g. as an enzyme inhibitor or as a toxin to kill a cancer cell. This book comprising of sixteen technical chapters, highlights the chemical and biological aspects of potential natural products with an intention of unravelling their pharmaceutical applicability in modern drug discovery processes. The synthesis, semi-synthesis and also biosynthesis of potentially bioactive natural products are covered. It also features chemical and biological advances in naturally occurring organic compounds describing their chemical transformations, mode of actions, and structure-activity relationships. 40 expert scientists from around the world report their latest findings and outline future opportunities for the development of novel and highly potent drugs based on natural products operating at the interface of chemistry and biology. This book is aimed at natural products chemists, medicinal chemists, biotechnologists, biochemists, pharmacologists, as well as the pharmaceutical and biotechnological industries.
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Veröffentlichungsjahr: 2015
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Table of Contents
Cover
Related Titles
Title Page
Copyright
Foreword
Preface
About the Editor
List of Contributors
Chapter 1: An Overview
1.1 Introduction
1.2 An Overview of the Book
1.3 Concluding Remarks
Chapter 2: Use of Chemical Genomics to Investigate the Mechanism of Action for Inhibitory Bioactive Natural Compounds
2.1 Introduction: Antibiotic Resistance and the Use of Natural Products as a Source for Novel Antimicrobials
2.2 Chemical Genetics and Genomics
2.3 Development of GDA Technology
2.4 Concluding Remarks
Abbreviations
References
Chapter 3: High-Throughput Drug Screening Based on Cancer Signaling in Natural Product Screening
3.1 Introduction
3.2 Cancer Signaling Pathways with Their Own Drug Screening Assays in HTS
3.3 Concluding Remarks
Abbreviations
References
Chapter 4: Immunosuppressants: Remarkable Microbial Products
4.1 Introduction
4.2 Discovery
4.3 Mode of Action
4.4 Biosynthesis
4.5 Genetics and Strain Improvement
4.6 Fermentation and Nutritional Studies
4.7 Other Activities of Immunosuppressants
4.8 Concluding Remarks
Acknowledgments
References
Chapter 5: Activators and Inhibitors of ADAM-10 for Management of Cancer and Alzheimer's Disease
5.1 Introduction to ADAM Family of Enzymes
5.2 ADAM-10 Structure and Physiological Roles
5.3 Pathological Significance
5.4 ADAM-10 as Potential Drug Target
5.5 Synthetic Inhibitors of ADAM-10
5.6 Natural Products as Activators and Inhibitors for ADAM-10
5.7 Natural Products as ADAM-10 Activators
5.8 Natural Products as ADAM-10 Inhibitors
5.9 Concluding Remarks
Abbreviations
References
Chapter 6: Structure and Biological Activity of Polyether Ionophores and Their Semisynthetic Derivatives
6.1 Introduction
6.2 Structures of Polyether Ionophores and Their Derivatives
6.3 Chemical Properties of Polyether Ionophores and Their Derivatives
6.4 Biological Activity
6.5 Concluding Remarks
Abbreviations
References
Chapter 7: Bioactive Flavaglines: Synthesis and Pharmacology
7.1 Introduction
7.2 Biosynthetic Aspects
7.3 Synthesis of Flavaglines
7.4 Pharmacological Properties of Flavaglines
7.5 Structure–Activity Relationships (SARs)
7.6 Concluding Remarks
Abbreviations
References
Chapter 8: Beneficial Effect of Naturally Occurring Antioxidants against Oxidative Stress–Mediated Organ Dysfunctions
8.1 Introduction
8.2 Oxidative Stress and Antioxidants
8.3 Concluding Remarks
Abbreviations
References
Chapter 9: Isoquinoline Alkaloids and Their Analogs: Nucleic Acid and Protein Binding Aspects, and Therapeutic Potential for Drug Design
9.1 Introduction
9.2 Isoquinoline Alkaloids and Their Analogs
9.3 Concluding Remarks
Acknowledgments
Abbreviations
References
Chapter 10: The Potential of Peptides and Depsipeptides from Terrestrial and Marine Organisms in the Fight against Human Protozoan Diseases
10.1 Introduction
10.2 Antiprotozoan Peptides and Depsipeptides of Natural Origin and Their Synthetic Analogs
10.3 Concluding Remarks
Abbreviations
References
Chapter 11: Sesquiterpene Lactones: A Versatile Class of Structurally Diverse Natural Products and Their Semisynthetic Analogs as Potential Anticancer Agents
11.1 Introduction: Structural Features and Natural Distribution
11.2 Anticancer Activity of Sesquiterpenes Lactones
11.3 Structure–Activity Relationships (SARs) of Sesquiterpenes Lactones
11.4 Concluding Remarks
Acknowledgments
Abbreviations
References
Chapter 12: Naturally Occurring Calanolides: Chemistry and Biology
12.1 Introduction
12.2 Naturally Occurring Calanolides: Structures and Physical Properties
12.3 Anti-HIV and Antituberculosis Potential of Calanolides
12.4 Total Syntheses of Calanolides
12.5 Concluding Remarks
Acknowledgment and Disclosure
Abbreviations
References
Chapter 13: Selective Estrogen Receptor Modulators (SERMs) from Plants
13.1 Introduction
13.2 Structure of Estrogen Receptor
13.3 Estrogen Receptor Signaling
13.4 Selective Estrogen Receptor Modulators from Plants
13.5 Molecular Basis of the Distinct SERM Action
13.6 SERMs in the Treatment of Estrogen-Mediated Cancers
13.7 Concluding Remarks
Abbreviations
References
Chapter 14: Introduction to the Biosynthesis and Biological Activities of Phenylpropanoids
14.1 Introduction
14.2 Biosynthesis of Phenylpropanoids
14.3 Some Phenylpropanoid Subclasses
14.4 Concluding Remarks
Acknowledgments
Abbreviations
References
Chapter 15: Neuropeptides: Active Neuromodulators Involved in the Pathophysiology of Suicidal Behavior and Major Affective Disorders
15.1 Introduction
15.2 Methods
15.3 Involvement of Neuropeptides in the Pathophysiology of Suicidal Behavior and Major Affective Disorders
15.4 The Association between Neuropeptides, Suicidality, and Major Affective Disorders
15.5 Discussion of the Main Findings
15.6 Concluding Remarks
Abbreviations
References
Chapter 16: From Marine Organism to Potential Drug: Using Innovative Techniques to Identify and Characterize Novel Compounds − a Bottom-Up Approach
16.1 Introduction
16.2 Structural Screening Approach
16.3 Testing for Bioactivity by Screening in Mammalian Cells
16.4 Chemical Genetics and Network Pharmacology in Yeast for Target Identification
16.5 Identification of Protein Targets by Proteomic Analysis on 2D Gels
16.6 Validation of Compound Targets by Biochemical Analysis
16.7 Next Steps in Drug Development
16.8 Concluding Remarks
Acknowledgments
Abbreviations
References
Chapter 17: Marine Natural Products: Biodiscovery, Biodiversity, and Bioproduction
17.1 Introduction
17.2 Biodiscovery: What and Where?
17.3 Biodiversity
17.4 From Biodiscovery to Bioproduction
17.5 Concluding Remarks
References
Index
EULA
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Guide
Cover
Table of Contents
Foreword
Preface
Chapter 1: An Overview
List of Illustrations
Figure 2.1
Figure 2.2
Figure 2.3
Figure 4.1
Figure 4.2
Figure 4.3
Figure 4.4
Figure 4.5
Figure 4.6
Figure 4.7
Figure 4.8
Figure 5.1
Figure 5.2
Scheme 6.1
Figure 6.1
Figure 6.2
Figure 6.3
Figure 6.4
Figure 6.5
Figure 6.6
Figure 6.7
Figure 6.8
Figure 6.9
Figure 6.10
Figure 6.11
Figure 6.12
Figure 6.13
Figure 6.14
Figure 6.15
Figure 6.16
Figure 6.17
Figure 6.18
Figure 6.19
Figure 6.20
Figure 6.21
Figure 6.22
Figure 6.23
Figure 6.24
Figure 6.25
Figure 6.26
Figure 6.27
Figure 6.28
Figure 6.29
Figure 6.30
Figure 6.31
Figure 6.32
Figure 6.33
Figure 6.34
Figure 6.35
Figure 6.36
Figure 6.37
Figure 6.38
Figure 6.39
Figure 6.40
Figure 6.41
Figure 6.42
Figure 6.43
Figure 6.44
Figure 7.1
Scheme 7.1
Scheme 7.2
Scheme 7.3
Scheme 7.4
Scheme 7.5
Scheme 7.6
Scheme 7.7
Scheme 7.8
Scheme 7.9
Scheme 7.10
Scheme 7.11
Scheme 7.12
Figure 7.2
Figure 7.3
Figure 8.1
Figure 8.2
Figure 8.3
Figure 8.4
Figure 8.5
Figure 8.6
Figure 8.7
Figure 8.8
Figure 8.9
Figure 8.10
Figure 8.11
Figure 8.12
Figure 8.13
Scheme 9.1
Scheme 9.2
Figure 9.1
Figure 9.2
Scheme 9.3
Scheme 9.4
Figure 9.3
Figure 9.4
Figure 9.5
Figure 9.6
Figure 9.7
Figure 9.8
Figure 9.9
Figure 9.10
Figure 9.11
Figure 11.1
Figure 11.2
Figure 11.3
Figure 11.4
Figure 11.5
Figure 11.6
Figure 11.7
Figure 11.8
Figure 11.9
Figure 11.10
Figure 11.11
Figure 12.1
Figure 12.2
Figure 12.3
Scheme 12.1
Scheme 12.2
Scheme 12.3
Scheme 12.4
Scheme 12.5
Scheme 12.6
Scheme 12.7
Scheme 12.8
Figure 13.1
Figure 13.2
Figure 13.3
Figure 13.4
Figure 13.5
Figure 13.6
Figure 14.1
Figure 14.2
Figure 14.3
Figure 14.4
Figure 14.5
Figure 14.6
Figure 15.1
Figure 15.2
Figure 15.3
Figure 15.4
Figure 15.5
Figure 15.6
Figure 15.7
Figure 15.8
Figure 15.9
Figure 15.10
Figure 15.11
Figure 15.12
Figure 15.13
Figure 15.14
Figure 15.15
Figure 15.16
Figure 16.1
Figure 16.2
Figure 16.3
Figure 16.4
Figure 16.5
Figure 16.6
Figure 16.7
Figure 16.8
Figure 16.9
Figure 16.10
Figure 16.11
Figure 17.1
Figure 17.2
Figure 17.3
Figure 17.4
Figure 17.5
List of Tables
Table 4.1
Table 5.1
Table 5.2
Table 5.3
Table 5.4
Table 5.5
Table 5.6
Table 5.7
Table 6.1
Table 6.2
Table 6.3
Table 6.4
Table 6.5
Table 6.6
Table 6.7
Table 6.8
Table 6.9
Table 7.1
Table 9.1
Table 9.2
Table 9.3
Table 9.4
Table 11.1
Table 12.1
Table 12.2
Table 17.1
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Edited by
Goutam Brahmachari
Bioactive Natural Products
Chemistry and Biology
The Editor
Prof. Dr. Goutam Brahmachari
Visva-Bharati University
Department of Chemistry
Santiniketan 732 235
India
All books published by Wiley-VCH are carefully produced. Nevertheless, authors, editors, and publisher do not warrant the information contained in these books, including this book, to be free of errors. Readers are advised to keep in mind that statements, data, illustrations, procedural details or other items may inadvertently be inaccurate.
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© 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Boschstr. 12, 69469 Weinheim, Germany
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Print ISBN: 978-3-527-33794-1
ePDF ISBN: 978-3-527-68441-0
ePub ISBN: 978-3-527-68442-7
Mobi ISBN: 978-3-527-68443-4
oBook ISBN: 978-3-527-68440-3
Foreword
Bioactive Natural Products: Chemistry and Biology edited by Professor (Dr.) Goutam Brahmachari and published by Wiley-VCH is a timely, highly significant, and useful book for readers engaged in chemical, biological, pharmacological, and medicinal study as well as research in these emerging areas.
Natural product science was one among the very few key areas of research in ancient times. Despite substantial progress in many other areas, research on natural product chemistry remains in the fuzzy region between chemical and biological research with undefined boundaries. It is argued that natural product chemistry is not a separate subject any longer: it is a hybrid discipline. In reality, the success in natural product research and its applications has opened up many other subdomains in science that are widely accepted in the academic world as well as in the modern chemical and pharmaceutical industries. For example, owing to the availability of many bioactive natural products, synthetic organic chemistry, computational chemistry, medicinal chemistry, biochemistry, and analytical chemistry as well as molecular biology, pharmacognosy, biotechnology, and clinical science have all become major areas of scientific research in recent decades. It has been extensively demonstrated that the search for natural products, or products obtained from natural sources through synthesis, is directed toward identifying new molecules for diseases and investigating their mechanisms of action and their specific targets of interaction (for example, DNA, RNA, proteins, and enzymes).
Natural products are classified on the basis of their origins, biological functions, and structures. Plants are a vast source of many natural drugs. A number of drugs are also synthesized from natural products through different chemical reactions. The most important of these natural products are terpenoids, alkaloids, steroids, phenolic compounds, vitamins, carbocyclics and hetrocyclic aromatic compounds, proteins, and carbohydrates. Bacteria and fungi are microorganisms that are also extremely useful in the search for and identification of organic molecules that have the potential to serve as drugs and highly active compounds. Many different drugs other than antibiotics have been isolated for medicinal use from microorganisms. Marine sources are relatively unexplored for the identification of bioactive compounds. However, there is considerable interest now in the isolation of novel molecules from various marine sources and the possibilities here are endless. The ocean is a huge source for natural biological and chemical products. In their search for natural products in the ocean's fish, snails, algae, sponges, reefs, bacteria, and microorganisms, it would appear that the journey of chemists and biologists to explore unknown, diverse, structurally unique, and potentially useful amazing naturally occurring molecules has only just begun. In addition to these sources, animals, venoms, and toxins are also screened for bioactive organic natural compounds.
Most of the natural products are found in combination with many other active or nonactive components. The first objective of research in natural product chemistry is to isolate, purify, determine the structure and structural alteration, and test these molecules as entities that can be used in medicine to enhance the quality of animal and human life. This is achieved through total or partial synthesis of bioactive natural products. In fact, the combined and tireless efforts of chemists and other scientists including clinicians have solved numerous complex medical problems through research on natural products. The second objective of research in this area is to study the mechanisms of action of natural products that may find use as drugs or lead molecules by identification of biochemical pathways using modern methods including genomic and proteomic analyses. The biodiversity of nature is available to us. Clearly, nature remains the most valuable source of chemical and biological investigation of molecules with novel stereochemistry. Therefore, new natural products and established bioactive natural products will remain a key for our well-being.
This book, edited by Professor Brahmachari, has a depth of knowledge and information. I believe expert scientists, researchers, and students will use this book for a tremendous learning and research experience. The quality and timeliness of this book in a market of competitive research will stimulate the present and future generations of scientists who are interested in improving the quality of human life through working on natural products and derivatives stemming from them. The book contains a wealth of features that include information on a diverse number of bioactive natural products presented by prominent authors with many pertinent references. This will help even persons without sufficient knowledge in natural products to undertake research in the area in the future.
The editor has a long history of publishing many books that have received tremendous scientific attention. The dedication of the editor in the selection of the authors, subject matter, and organization of the chapters proves his experience and scholarly activity in this particular area. He has chosen numerous contributors who are active in this specific field. Each chapter is presented in a highly elegant and precise manner. Scientists working on natural product chemistry will find this a handy resource book that will help them with their work. The enduring work of many scientists on biologically active natural products in the isolation, detection, and structure elucidation along with biological study as described in the content of every chapter will prove to be very useful for the current and future generations of scientists.
I strongly recommend this state-of-the-art book on the chemistry and biology of bioactive natural products to students and researchers who are engaged in natural product research as well as synthesis and biological evaluation of novel molecules for different types of medical disorders and for those who are pursuing their activities to improve the quality of our lives.
Bimal K. Banik
The University of Texas-Pan American
Edinburg, USA
Preface
This single volume entitled Bioactive Natural Products: Chemistry and Biology is an endeavor to focus the recent cutting-edge research advances in the field of bioactive natural products, very particularly operating at the interface of chemistry and biology, and also to underline how natural product research continues to make significant contributions in the domain of discovery and development of new medicinal entities. This book consists of a total of 17 chapters contributed by eminent researchers from several countries in response to my personal invitation. I am most grateful to the contributors for their generous and timely response in spite of their busy and tight schedules with academics, research, and other responsibilities.
Natural products usually refer to chemical substances produced by a living organism or found in nature that have distinctive biological and pharmacological effects; they encompass a wide variety of chemical compound classes, including alkaloids, antibiotics, terpenoids, flavonoids, xanthonoids, phenolics, carbohydrates, lipids, proteins and amino acids, and nucleic acids. The huge diversity in chemical structures of natural products is an outcome of biosynthetic processes that have been modulated over the millennia through genetic effects. Such chemical entities have played a crucial role in modern drug development and still constitute a prolific source of novel lead compounds, or pharmacophores, for ongoing drug discovery programs. Most significantly, natural products operate at the interface of chemistry and biology. Hence, search for bioactive molecules from nature (plants, animals, microflora) continues to play an important role in fashioning new medicinal agents. With the advent of modern techniques, very particularly the rapid improvements in spectroscopic as well as accompanying advances in high-throughput screening techniques, it has become possible to have an enormous repository of bioactive natural compounds, thus opening up exciting new opportunities in the field of new drug development to the pharmaceutical industry.
Medicinal chemistry of such bioactive compounds encompasses a vast area that includes their isolation and characterization from natural sources; structure modification for optimization of their activity and other physical properties; and also total and semisynthesis for a thorough scrutiny of structure–activity relationships. It has been well documented that natural products played a significant role in modern drug development, especially for antibacterial and antitumor agents; however, their uses in the treatment of other epidemics such as AIDS and cardiovascular, cancerous, neurodegradative, infective, and metabolic diseases have also been extensively explored. The need for leads to solve such health problems threatening the world population makes all natural sources important for the search of novel molecules, diversified and unique structural architectures of which inspired scientists to pursue new chemical entities with completely different structures from known drugs. Researchers around the globe are deeply engaged in exploring the detailed chemistry, pharmacology, and biology of such potent and naturally occurring efficacious bioactive compounds. Current research trends in the field suggest an optimistic future for natural products in drug discovery; however, novel strategies and innovative approaches in addition to the introduction of more sophisticated technical requirements are still needed today for the development of natural products into new drugs.
This book, which comprises a variety of 17 chapters written by active researchers and leading experts working in the field of chemistry of biologically active natural products, brings together an overview of current discoveries and trends in this remarkable field. Chapter 1 presents an overview of the book and summarizes the contents of the other chapters so as to offer glimpses of the subject matter covered to the readers before they go in for a detailed study. Chapters 2 through 17 are devoted to exploring the ongoing chemical, biological, and pharmacological advances in naturally occurring organic compounds and describe their biosynthesis, semisynthesis, total synthesis, chemical transformations, structure–activity relationships, nucleic acid and protein-binding aspects, biodiversity, and bioproduction, including mechanism of action, high-throughput drug screening, and drug design.
This timely volume encourages interdisciplinary work among chemists, biologists, pharmacologists, botanists, and agronomists with an interest in bioactive natural products. It is also an outstanding source of information with regard to the industrial application of natural products for medicinal purposes. The broad interdisciplinary approach dealt with in this book would surely make the work much more interesting for scientists deeply engaged in the research and/or use of bioactive natural products. It will serve as a valuable resource for researchers in their own fields not only to predict promising leads for developing pharmaceuticals to treat various ailments and disease manifestations but also to motivate young scientists to the dynamic field of bioactive natural products research.
Representation of facts and their discussions in each chapter are exhaustive, authoritative, and deeply informative; hence, the book would serve as a key reference for recent developments in the frontier research on bioactive natural products at the interface of chemistry and biology, and would also be of much utility to scientists working in this area. I would like to express my sincere thanks once again to all the contributors for the excellent reviews on the chemistry, biology, and pharmacology of bioactive natural products. It is their participation that makes my effort to organize such a book possible. Their masterly accounts will surely provide the readers with a strong awareness of current cutting-edge research approaches being followed in some of the promising fields of biologically active natural products.
I would like to express my sincere thanks and deep sense of gratitude to Professor Bimal K. Banik, Department of Chemistry, The University of Texas-Pan American, United States, for his keen interest in the manuscript and for writing foreword to the book.
Finally, I would like to express my deep sense of appreciation to all of the editorial and publishing staff members associated with Wiley-VCH, Weinheim, Germany, for their keen interest in publishing the work and also for their all-round help so as to ensure that the highest standards of publication are maintained in bringing out the book.
October 2014
Goutam Brahmachari
Visva-Bharati University
Chemistry Department
Santiniketan, India
About the Editor
Professor (Dr.) Goutam Brahmachari was born at Barala in the district of Murshidabad (West Bengal), India, on April 14, 1969. He received his high school degree in scientific studies in 1986 at Barala R. D. Sen High School under the West Bengal Council of Higher secondary Education (WBCHSE). Then he moved to Visva-Bharati (a central University founded by Rabindranath Tagore at Santiniketan, West Bengal, India) to study chemistry at the undergraduate level. After graduating from this University in 1990, Prof. Brahmachari completed his masters in 1992 with specialization in organic chemistry and thereafter received his Ph.D. degree in 1997 in chemistry from the same University. He was appointed as assistant professor of organic chemistry at Visva-Bharati University, Department of Chemistry, in 1998, then became associate professor in 2008. In 2011, he became full professor of organic chemistry in the same faculty. At present, he is responsible for teaching courses in organic chemistry, natural products chemistry, and physical methods in organic chemistry. Several students have received their Ph.D. degree under the supervision of Prof. Brahmachari during this period, and a couple of research fellows are presently working with him both in the fields of natural products and synthetic organic chemistry. He serves as a member of the Indian Association for the Cultivation of Science (IACS) and Indian Science Congress Association (ISCA), Kolkata. He also serves as an Editor-in-Chief, Signpost Open Access Journal of Organic and Biomolecular Chemistry, and as editorial board member of several journals.
Prof. Brahmachari's research interests include (i) isolation, structural determination, and/or detailed NMR study of new natural products from medicinal plants; (ii) synthetic organic chemistry with special emphasis on green chemistry; (iii) semisynthetic studies with natural products; and (iv) evaluation of biological activities and pharmacological potential of natural and synthetic compounds. With more than 16 years of teaching experience, he has produced so far nearly 120 publications including original research papers, review articles, and invited book chapters in edited books in the field of natural products and organic synthesis from internationally reputed presses. Prof. Brahmachari has authored/edited a number of text and reference books that include Organic Name Reactions: A Unified Approach (Narosa Publishing House, New Delhi; Co-published by Alpha Science International, Oxford, 2006), Chemistry of Natural Products: Recent Trends & Developments (Research Signpost, 2006), Organic Chemistry Through Solved Problems (Narosa Publishing House, New Delhi; Co-published by Alpha Science International, Oxford, 2007), Natural Products: Chemistry, Biochemistry and Pharmacology (Narosa Publishing House, New Delhi; Co-published by Alpha Science International, Oxford, 2009), Handbook of Pharmaceutical Natural Products–2 volume-set (Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim, Germany, 2010), Bioactive Natural Products: Opportunities & Challenges in Medicinal Chemistry (World Scientific Publishing Co. Pte. Ltd., Singapore, 2011), Chemistry and Pharmacology of Naturally Occurring Bioactive Compounds (CRC Press, Taylor & Francis group, USA, 2013), and Natural Bioactive Molecules: Impacts & Prospects (Narosa Publishing House, New Delhi; Co-published by Alpha Science International, Oxford, 2014), Green Synthetic Approaches for Biologically Relevant Heterocycles (Elsevier Inc., USA, 2014).
He is regularly consulted as a referee by leading international journals including Elsevier, Royal Society of Chemistry, American Chemical Society, Wiley, Taylor & Francis, Springer, Bentham Science, Indian Chemical Society, Korean Chemical Society, Brazilian Chemical Society, Bulgarian Academy of Sciences and so on, and also various financial commissions.
Goutam Brahmachari enjoys songs of Rabindranath Tagore, and finds interests in Literature as well!
List of Contributors
Mario Amore
University of Genoa
Maternal and Child Health
Section of Psychiatry
Department of Neuroscience
Rehabilitation
16126 Genoa
Italy
Michal, Antoszczak
Adam Mickiewicz University in Poznań
Department of Bioorganic Chemistry
Faculty of Chemistry
ul Umultowska 89b
61-614 Poznań
Poland
Paul H. Atkinson
Victoria University of Wellington
Centre for Biodiscovery
School of Biological Sciences
PO Box 600
Wellington 6140
New Zealand
Christine Basmadjian
CNRS/University of Strasbourg
Therapeutic Innovation Laboratory (UMR 7200)
Faculty of Pharmacy
Route du Rhin
Illkirch Cedex
France
and
AAREC Filia Research
Place Paul Verlaine
Boulogne-Billancourt
France
Goutam Brahmachari
Visva-Bharati (a Central University)
Laboratory of Natural Products and Organic Synthesis
Department of Chemistry
Siksha Bhavana
Birbhum
Santiniketan
West-Bengal 731 235
India
Lena Brundin
Michigan State University
College of Human Medicine
Department of Psychiatry and Behavioral Medicine
Grand Rapids
48824
USA
and
Van Andel Research Institute
Laboratory of Behavioral Medicine
Grand Rapids
Michigan
USA
Daniel Burnside
Carleton University
Ottawa Institute of Systems Biology
Department of Biology
Ottawa
ON K1S 5B6
Canada
Ricardo Calado
Universidade de Aveiro
Departamento de Biologia & CESAM
Campus Universitário de Santiago
3810-193 Aveiro
Portugal
Devdutt Chaturvedi
Amity University Uttar Pradesh
Laboratory of Medicinal Chemistry
Amity Institute of Pharmacy
Lucknow
UP 226028
India
Arnold L. Demain
Drew University
Research Institute for Scientists Emeriti (R.I.S.E.)
Madison, NJ 07940
USA
Laurent Désaubry
CNRS/University of Strasbourg
Therapeutic Innovation Laboratory (UMR 7200)
Faculty of Pharmacy
Route du Rhin
Illkirch Cedex
France
Yuping Du
Lanzhou University
School of Life Science
Tianshui Road 222
Lanzhou City
Gansu 730000
P.R China
Parmesh Kumar Dwivedi
Amity University Uttar Pradesh
Laboratory of Medicinal Chemistry
Amity Institute of Pharmacy
Lucknow
UP 226028
India
Yogesh Dwivedi
University of Alabama at Birmingham
Department of Psychiatry and Behavioral Neurobiology
Birmingham, AL 35233
USA
Sandrine Faivre
Beaujon University Hospital
INSERM U728/AP-HP
Department of Medical Oncology
Clichy
France
Ângelo de Fátima
Universidade Federal de Minas Gerais
Grupo de Estudos em Química Orgânica e Biológica (GEQOB)
ICEx
Departamento de Química
MG 31270-901 Belo Horizonte
Brazil
Jessica J. Field
Victoria University of Wellington
Centre for Biodiscovery
School of Biological Sciences
PO Box 600
Wellington 6140
New Zealand
Jean Fotie
Southeastern Louisiana University
Department of Chemistry and Physics
SLU 10878
Hammond, LA 70402-0878
USA
Shatadal Ghosh
Division of Molecular Medicine
Bose Institute
P-1/12
CIT Scheme VII M
Kolkata
West Bengal 700054
India
Paolo Girardi
Sapienza University of Rome
Department of Neurosciences
Mental Health and Sensory Organs
Sant'Andrea Hospital
1035-1039 Via di Grottarossa
Rome
Italy
Ashkan Golshani
Carleton University
Ottawa Institute of Systems Biology
Department of Biology
Ottawa
ON K1S 5B6
Canada
Armand de Gramont
AAREC Filia Research
Place Paul Verlaine
Boulogne-Billancourt
France
and
Beaujon University Hospital
INSERM U728/AP-HP
Department of Medical Oncology
Clichy
France
Manas K. Haldar
North Dakota State University
Department of Pharmaceutical Sciences
Albrecht Boulevard
Fargo, ND 58108
USA
Mohsen Hooshyar
Carleton University
Ottawa Institute of Systems Biology
Department of Biology
Ottawa
ON K1S 5B6
Canada
Adam Huczyński
Adam Mickiewicz University in Poznań
Department of Bioorganic Chemistry
Faculty of Chemistry
ul Umultowska 89b
61-614 Poznań
Poland
Prajakta Kulkarni
North Dakota State University
Department of Pharmaceutical Sciences
Albrecht Boulevard
Fargo, ND 58108
USA
Gopinatha S. Kumar
CSIR-Indian Institute of Chemical Biology
Biophysical Chemistry Laboratory
Chemistry Division
4, Raja S.C. Mullick Road
Kolkata 700 032
India
Divya Lakshmanan Mangalath
Department of Biotechnology and Microbiology
Kannur University
Thalassery Campus
Palayad P.O.
Kerala-670661
India
Miguel C. Leal
Universidade de Aveiro
Departamento de Biologia & CESAM
Campus Universitário de Santiago
3810-193 Aveiro
Portugal
and
University of Georgia
Skidaway Institute of Oceanography
Ocean Science Circle
Savannah, GA 31411
USA
Daniel Lindqvist
Lund University
Department of Clinical Sciences
Section for Psychiatry
Baravăgen 1, SE-221 85
Lund
Sweden
Sanku Mallik
North Dakota State University
Department of Pharmaceutical Sciences
Albrecht Boulevard
Fargo, ND 58108
USA
Imelda G. Marquez
Carleton University
Ottawa Institute of Systems Biology
Department of Biology
Ottawa
ON K1S 5B6
Canada
John H. Miller
Victoria University of Wellington
Centre for Biodiscovery
School of Biological Sciences
PO Box 600
Wellington 6140
New Zealand
Mamta Mishra
Food and Drug Administration
Government Public Analytical Laboratory
Lucknow
UP 226024
India
Luzia V. Modolo
Universidade Federal de Minas Gerais
Grupo de Estudos em Bioquímica de Plantas (GEBioPlan)
Departamento de Botânica
MG 31270-901 Belo Horizonte
Brazil
Houman Moteshareie
Carleton University
Ottawa Institute of Systems Biology
Department of Biology
Ottawa
ON K1S 5B6
Canada
Canan G. Nebigil
CNRS/University of Strasbourg
Biotechnology and Cell Signaling Laboratory (UMR7242)
Illkirch Cedex
France
Peter T. Northcote
Victoria University of Wellington
Centre for Biodiscovery
School of Chemical and Physical Sciences
PO Box 600
Wellington 6140
New Zealand
Katayoun Omidi
Carleton University
Ottawa Institute of Systems Biology
Department of Biology
Ottawa
ON K1S 5B6
Canada
Pabitra B. Pal
Bose Institute
Division of Molecular Medicine
P-1/12
CIT Scheme VII M
Kolkata
West Bengal 700054
India
Harry E. Peery
McMaster University
Division of Reproductive Biology
Department of Obstetrics and Gynecology
Hamilton
ON L8S 4L8
Canada
Eric Raymond
Beaujon University Hospital
INSERM U728/AP-HP
Department of Medical Oncology
Clichy
France
Caroline Robert
Gustave Roussy Institute
INSERM U981 and Department of Dermato-Oncology
Villejuif
France
Jacek Rutkowski
Adam Mickiewicz University in Pozna\'{n}
Department of Bioorganic Chemistry
Faculty of Chemistry
ul Umultowska 89b
61-614 Poznań
Poland
Chittalakkottu Sadasivan
Department of Biotechnology and Microbiology
Kannur University
Thalassery Campus
Palayad P.O.
Kerala-670661
India
Bahram Samanfar
Carleton University
Ottawa Institute of Systems Biology
Department of Biology
Ottawa
ON K1S 5B6
Canada
Gianluca Serafini
Sapienza University of Rome
Department of Neurosciences
Mental Health and Sensory Organs~\endash ~Suicide Prevention Center
Sant'Andrea Hospital
1035-1039 Via di Grottarossa
Rome
Italy
Maria Serova
AAREC Filia Research
Place Paul Verlaine
Boulogne-Billancourt
France
and
Beaujon University Hospital
INSERM U728/AP-HP
Department of Medical Oncology
Clichy
France
Kristina Shostak
Carleton University
Ottawa Institute of Systems Biology
Department of Biology
Ottawa
ON K1S 5B6
Canada
Parames C. Sil
Division of Molecular Medicine
Bose Institute
P-1/12
CIT Scheme VII M
Kolkata
West Bengal 700054
India
Cristiane J. da Silva
Universidade Federal de Minas Gerais
Grupo de Estudos em Bioquímica de Plantas (GEBioPlan)
Departamento de Botânica
MG 31270-901 Belo Horizonte
Brazil
Fernanda G. da Silva
Universidade Federal de Minas Gerais
Grupo de Estudos em Bioquímica de Plantas (GEBioPlan)
Departamento de Botânica
MG 31270-901 Belo Horizonte
Brazil
Leonardo da Silva Neto
Universidade Federal de Minas Gerais
Grupo de Estudos em Química Orgânica e Biológica (GEQOB)
Departamento de Química
MG 31270-901 Belo Horizonte
Brazil
A. Jonathan Singh
Victoria University of Wellington
Centre for Biodiscovery
School of Chemical and Physical Sciences
PO Box 600
Wellington 6140
New Zealand
Myron L. Smith
Carleton University
Ottawa Institute of Systems Biology
Department of Biology
Ottawa
ON K1S 5B6
Canada
Stephan Vagner
Gustave Roussy Institute
INSERM U981 and Department of Dermato-Oncology
Villejuif
France
Preeti Vaishnav
C-3101 Rustomjee Elanza C.H.S.
Mind Space
Malad (W)
Mumbai 400064
India
Jinbo Yang
Lanzhou University
School of Life Science
Tianshui Road 222
Lanzhou City
Gansu 730000
P.R China
and
The Cleveland Clinic
Lerner Research Institute
Department of Molecular Genetics
Cleveland, OH 44195
USA
Young J. Yoo
Ewha Womans University
Department Chemistry and Nano Science
Seoul 120-750
Korea
Yeo J. Yoon
Ewha Womans University
Department Chemistry and Nano Science
Seoul 120-750
Korea
Xinxin Zhang
Lanzhou University
School of Life Science
Tianshui Road 222
Lanzhou City
Gansu 730000
P.R China
Qian Zhao
CNRS/University of Strasbourg
Therapeutic Innovation Laboratory (UMR 7200)
Faculty of Pharmacy
Route du Rhin
Illkirch Cedex
France
and
AAREC Filia Research
Place Paul Verlaine
Boulogne-Billancourt
France
1An Overview
Goutam Brahmachari
1.1 Introduction
The endeavor of this book entitled Bioactive Natural Products: Chemistry and Biology is to present details of cutting-edge research in the chemistry and biology of bioactive natural products and it helps the reader understand how natural product research continues to make significant contributions in the discovery and development of new medicinal entities. This is a reference book meant for phytochemists, synthetic chemists, combinatorial chemists, as well as other practitioners and advanced students in related fields. The book, comprising of 16 technical chapters, highlights the chemical and biological aspects of potential natural products with an intention to unravel their pharmaceutical applicability in modern drug discovery processes. The book covers the synthesis, semisynthesis as well as biosynthesis of potentially bioactive natural products. It also features chemical and biological advances in naturally occurring organic compounds, describing their chemical transformations, modes of action, and structure–activity relationships.
This introductory chapter (Chapter 1) presents an overview of the book, and summarizes the contents and subject matter of each chapter so as to offer certain glimpses of the coverage of discussion to the readers before they go for detailed study.
1.2 An Overview of the Book
The present book contains a total of 16 technical chapters – Chapters 2–17; this section summarizes the contents and subject matter of each of these chapters.
1.2.1 Chapter 2
In Chapter 2, Golshani and his group have discussed the use of chemical genomics to investigate the mechanism of action (MOA) for inhibitory bioactive natural compounds. Understanding the specific MOA of small molecules is considered one of the most significant hurdles in developing new drugs. Traditional pathway-specific mechanistic approaches are time consuming and expensive. Global genome-wide single-deletion array (GDA) technology nowadays provides a more feasible alternative to laborious metabolic pathway-specific assays and has the added advantage of working on a global scale. The use of GDA technology to screen natural substances for intriguing inhibitory compounds can help probe the biological complexity of intracellular networks or identify leads for promising novel antimicrobials. GDA technology can both identify direct target and off-target effects of a novel compound or expand our understanding of previously studied compounds. This illuminating and useful chapter offers an extensive overview on the use of GDAs in Saccharomyces cerevisiae and Escherichia coli as well as combinatorial haploinsufficiency mutant profiling/homozygous mutant profiling (HIP/HOP) as genomic tools to investigate MOA in naturally derived inhibitory compounds. The present chapter offers an impetus to the practitioners deeply engaged in this remarkable field.
1.2.2 Chapter 3
Yang and his group have discussed on the application of high-throughput screening (HTS) of potential natural products based on cancer-signaling strategies including EGFR, P13K, Wnt, and STATs in Chapter 3. With the advances in molecular biology, human genetics, and functional genomics, HTS involves continuous invention and improvement in methods. With the assay of HTS, targeting the cancer-signaling pathways has experienced a more significant impact on drug discovery and development in recent times. More attentions is being focused on the selection of cancer molecular targets between generality and specificity, that is, cell proliferation and survival peculiar to a tumor and anticancer drug research with advanced HTS assays is expected to be a revolutionary technological advance in coming years. The present chapter would surely motivate researchers working in this area of interest.
1.2.3 Chapter 4
Chapter 4, by Demain and his group, is dedicated to potential microbial immunosuppresssants including antifungal peptides and antibiotics cyclosporin, tacrolimus, sirolimus, mycophenolic acid, and ascomycin. Discovery, fermentation, strain improvement, mode of action, and biosynthesis of the representative immunosuppressants are discussed in detail. The biosynthetic pathway of such microbial products involves a series of complex reactions carried out by multienzyme polypeptides that catalyze reactions in a belt-like manner, first forming a chain, then undergoing elongation and cyclization. Genes encoding these enzymes have been cloned and studied as well. The present chapter highlights the applications of immunosuppressants not only in organ transplantation, but also in the treatment of many other life-threatening diseases such as autoimmune disorders, cancer, AIDS, asthma, skin diseases, respiratory ailments, and malaria. Continuing research offering more insights into the genetics, biosynthesis, and molecular mode of action of these drugs would open new windows for their further applications as effective therapeutics. This illuminating review on immunosuppressants would obviously enrich the readers and would motivate them in undertaking in-depth research in immunosuppressants coupled with medicinal chemistry.
1.2.4 Chapter 5
In Chapter 5, Mallik and his group have presented a comprehensive discussion on the activators and inhibitors of ADAM-10 for management of cancer and Alzheimer's disease. A disintegrin and metalloproteinase (ADAM) family of proteolytic enzymes is known for “shedding” of membrane-bound proteins and are unique among cell surface proteins as they possess an adhesion domain and a protease domain. The deviation from normal levels of ADAMs is also observed in various pathological conditions such as cancer and Alzheimer's disease. The enzyme is downregulated in Alzheimer's disease while over-expressed in various cancers. Involvement of ADAM-10 in progression of cancer and Alzheimer's disease is now well established. Compounds from natural and synthetic origins involved in selective activation or inhibition of ADAM-10 possess tremendous potential as therapeutics for treating cancer and Alzheimer's disease. The present chapter offers an up-to-date development in this field.
1.2.5 Chapter 6
Chapter 6, by Huczyński and his group, deals with the structure and biological activity of polyether ionophores and their semisynthetic derivatives. Polyether ionophores, which belong to a large group of antibiotics, are unique natural compounds because they exhibit a broad spectrum of biological activities including antibacterial, antiviral, and anticancer activity. Natural polyether ionophores have been found to exhibit potent activity against those cancer cells that display multidrug resistance (MDR) and also against cancer stem cells (CSCs). It has been demonstrated that biological potency of such polyether ionophores is related to their unique chemical structure, as well as their ability to form complexes with mono- and divalent metal cations facilitating their transport across lipid membranes. This phenomenon results in a disturbance of the natural cation concentration gradient and intracellular pH change, leading to mitochondrial injury, cell swelling, and vacuolization and, as a consequence, programmed cell death (apoptosis). The authors have discussed all these issues in detail in the present chapter highlighting their structural and chemical properties, semisynthetic derivatives, and the mechanisms of cation transport.
1.2.6 Chapter 7
Désaubry and coauthors have reviewed the synthesis and pharmacology of bioactive flavaglines in Chapter 7. Flavaglines represent a family of cyclopenta[b]benzofurans found in medicinal plants of the genus Aglaia, and have been reported to display potent anti-inflammatory, neuroprotective, cardioprotective, and anticancer activities. It has been revealed that flavaglines have the ability to kill cancer cells without affecting normal cells. Such a selective cytotoxicity to cancer cells and cytoprotection to normal cells, both of which occur at nanomolar concentrations, is unprecedented. In the present chapter, the authors have offered an excellent overview on the synthetic routes to flavaglines, MOA, and evaluation of biological potency of the target compounds with the objective of discovering certain novel therapeutic agents from this class of bioactive natural products.
1.2.7 Chapter 8
In Chapter 8, Sil and his group have described the beneficial effect of naturally occurring antioxidants against oxidative stress-mediated organ dysfunctions. The metabolism of oxygen by cells generates potentially harmful reactive oxygen species (ROSs). In recent times, oxidative stress or imbalance between pro-oxidants and antioxidants is a comparatively new issue that has extensively troubled research in biomedical sciences. It has now been established that it significantly contributes to the pathophysiology of various prevalent diseases such as hypertension, diabetes, asthma, allergies, autism, lupas, acute renal failure, atherosclerosis, rheumatoid, Alzheimer's, Parkinson's, and cardiovascular diseases. Oxidative stresses in the cells have a considerable impact leading to defective cellular function, aging, or disease. Consequently, a better thoughtful role of ROS-mediated signaling in normal cellular function as well as in disease is necessary for developing therapeutic tools for oxidative stress-related pathogenesis. The present chapter has a detailed discussion on the multifunctional therapeutic applications and signaling properties of naturally occurring antioxidants, which obviously play a number of beneficial roles in oxidative stress-induced organ dysfunctions. The authors have been successful in unraveling the potential use of naturally occurring antioxidants as novel promising therapeutic strategies.
1.2.8 Chapter 9
Chapter 9, by Gopinatha Suresh Kumar, deals with the nucleic acid and protein-binding aspects of isoquinoline alkaloids and their analogs, and their therapeutic potential for drug design. Isoquinoline alkaloids and analogs represent an important class of molecules that have attracted attention for their various potential pharmacological activities. Specific binding to cellular biomacromolecules such as DNA and RNA has been thought to be one of the most important routes for their therapeutic action. In this chapter, an up-to-date knowledge on the binding aspects of some of the most important isoquinoline alkaloids and their analogs are presented. Elucidation of the recognition mechanism and accumulation of a large volume of recent research outcomes have been covered in the present chapter, which serves as a useful guide to researchers working in the development of potential therapeutic agents.
1.2.9 Chapter 10
Jean Fotie has presented an exhaustive discussion on the potential of peptides and depsipeptides from terrestrial and marine organisms in the fight against human protozoan diseases such as malaria, trypanosomiasis, leishmaniasis, amebiasis, toxoplasmosis, cryptosporidiosis, sarcocystis, coccidiosis, babesiosis, and giardiasis in Chapter 10. Peptides and depsipeptides are a widely distributed family of naturally occurring molecules, usually found in fungi, actinomycetes, cyanobacteria, higher plants, and marine organisms, with a broad window of biological and pharmacological activities ranging from antibacterial to anticancer, some of which are currently in clinical use or have entered human clinical trials as antibiotic or anticancer agents. This family of compounds should be given a serious and careful consideration for their antiprotozoan activity. The present chapter would act as a stimulus in this direction.
1.2.10 Chapter 11
Chapter 11, by Chaturvedi and his group, is devoted to naturally occurring sesquiterpene lactones and their semisynthetic analogs as potential anticancer agents. Wide structural diversity coupled with potential biological activities of sesquiterpene lactones has attracted a great deal of attention from medicinal chemists around the world. Although, the exact MOA of SLs is not well known, it has been documented through various published reports that the biological activity displayed by majority of sesquiterpene lactones is due to the presence of α-methylene-γ-lactones and the α,β-unsaturated cyclopentenone ring. In the present chapter, the authors have focused on an up-to-date and comprehensive account on the sesquiterpenes lactones as anticancer agents.
1.2.11 Chapter 12
Brahmachari has focused on the chemistry and biology of naturally occurring calanolides in Chapter 12. Natural calanolides occupy a significant position in the pyranocoumarin class of compounds, and are well known for their anti-HIV potential. In addition, these pyrnocoumarins have also been found to exhibit antituberculosis activity as well. Such promising pharmaceutical activity coupled with low availability of natural calanolides has evoked tremendous interest among the organic chemists to undertake systematic chemical studies toward the total synthesis of this class of compounds. Preclinical and clinical results of both natural and synthetic calanolides have been found to be quite encouraging, and consequently they are being regarded as potential “leads” in the development of future anti-HIV and antituberculosis drugs. The present chapter covers up-to-date literature of naturally occurring calanolides in view of their anti-HIV and antituberculosis potential, their chemical analogs, and total syntheses.
1.2.12 Chapter 13
Chapter 13, by Lakshmanan and Sadasivan, deals with certain plant-derived selective estrogen receptor modulators (SERMs). Phytoestrogens are markedly similar in chemical structure to the mammalian estrogen and estradiol; they and bind to estrogen receptors, with a preference for ERβ. Different physiological functions of the body such as reproduction, behavior, and neuroendocrine function are regulated by estrogen through estrogen receptor subtypes. These receptors have tissue-specific functions with respect to each other. For example, ERα induces cell proliferation, whereas ERβ antagonizes this action. Thus, their differential expression and activation in a balanced manner is necessary for normal functioning of the body and any imbalance in this expression leads to oncogenesis and several autoimmune diseases. Hence, phytoestrogens which mimic the function of endogenous estrogen can be judiciously exploited for regulating this imbalance and reverting back the normal functions of the body. SERMs may, thus be considered as potential lead compounds for the development of drugs in the treatment of estrogen-mediated cancers and autoimmune diseases. The present chapter would be very useful to readers whose interests lie in the study of potential phytoestrogens.
1.2.13 Chapter 14
Modolo and her group have discussed biosynthesis and biological activities of phenylpropanoids in Chapter 13. Phenylpropanoids compounds, which bear a C6–C3 phenolic scaffold, have received particular attention not only because of their function in plants but also because of their wide spectrum of biological activities. Flavonoids, coumarins, and stilbenes have been considered as the main subclass of phenylpropanoids in the present discussion. This illuminating overview provides valuable information about the biosynthesis and pharmacological potential of such medicinally important phenylpropanoid compounds.
1.2.14 Chapter 15
Chapter 15 by Serafini and his group is devoted to neuropeptides which are the active neuromodulators involved in the pathophysiology of suicidal behavior and major affective disorders. Neuropeptidergic circuits seem to act as fundamental mediators of human behavior. These molecules may represent interesting mediators of stress-related disorders, major affective conditions, and suicidal behavior. From their detailed literature survey, it has been demonstrated that there remains an association between suicidality and corticotrophin-releasing factor (CRF), nerve growth factor (VGF), cholecystokinin (CCK), orexin, substance P, and Neuropeptide Y (NPY); these molecules play a key role in many biological functions and act as important neuromodulators of emotional processing. Although many studies identified a positive association between neuropeptide alterations and major depressive disorders/suicidal behavior, it is, however, unlikely that neuropeptides may currently represent definitive biomarkers of suicidality/depression. Further studies are needed in order to elucidate the complex nature of neuropeptidergic abnormalities underlying suicidal behavior and major affective conditions. The authors of this present chapter have performed the job in this direction to offer an insight into the cause and the search for possible remedies.
1.2.15 Chapter 16
Chapter 16 by Miller and his group is devoted to the discussion on some innovative techniques to identify and characterize novel compounds from marine organisms as potential drug molecules. Marine organisms are a rich source of natural products, having potential as lead compounds in drug discovery. The path from discovery of a novel compound to clinical use, however, is a long and complex one in which many lead structures drop out along the way. In the present chapter, the authors have focused on the approach used in their chemistry and biology laboratories to find new biologically active compounds (NMR-based screening) along with providing clues on their mode of action (chemical genetics and proteomics), and validation of their effects in mammalian cells (biochemical analysis of target responses). This chapter would provide useful information to researchers deeply involved in the drug discovery process.
1.2.16 Chapter 17
Chapter 17, by Leal and Calado, deals with the biodiscovery, biodiversity, and bioproduction of marine natural products (MNPs). MNPs are acknowledged as the “blue gold,” as they hold a vast reservoir of promising leads for drug development. Critical survey of literature on the biodiscovery, biodiversity, and bioproduction of MNPs reveals that although new technologies have promoted significant advances in the collection, screening, and identification of a whole new range of molecules, marine chemical ecology is still several decades behind its terrestrial counterpart; there is still a vast fraction of marine biodiversity yet to be screened, as well as regions in the world's oceans that remain poorly explored. In this chapter, the authors have overviewed past and current trends of MNP biodiscovery, both taxonomically and geographically, and discuss them in view of marine biodiversity and biogeography. In addition, they have also discussed the bioproduction of secondary metabolites of marine organisms, particularly through in toto aquaculture.
1.3 Concluding Remarks
This introductory chapter summarizes the technical chapters of this book, each of which is exhaustive in its representation of facts and with discussions that are authoritative and deeply informative. The readers will find discussions that provoke interest in each of the chapters, which practically cover wide area of bioactive natural product research, particularly on their chemical and biological aspects. The references encourage interdisciplinary work among chemists, pharmacologists, biologists, botanists, and agronomists with an interest in bioactive natural products. Hence, the present book should definitely serve as a key reference for recent developments in frontier research on bioactive natural products, and also would find much utility for the scientists working in this area.
2Use of Chemical Genomics to Investigate the Mechanism of Action for Inhibitory Bioactive Natural Compounds1
Daniel Burnside, Houman Moteshareie, Imelda G. Marquez, Mohsen Hooshyar, Bahram Samanfar, Kristina Shostak, Katayoun Omidi, Harry E. Peery, Myron L. Smith and Ashkan Golshani
2.1 Introduction: Antibiotic Resistance and the Use of Natural Products as a Source for Novel Antimicrobials
A significant fraction of current therapeutic agents for all diseases were originally derived from natural sources. Between 1981 and 2006, 45% of newly approved small molecule drugs were either natural products or a derivative/mimic of a natural product [1]. Naturally derived compounds are a promising source of new antibiotic scaffolds which have not yet seen induced resistance develop [2]. Given the immense number of bioactive natural compounds found in nature, cost- and time-permissible assays which help to characterize strong leads are crucial when sifting through expanding chemical libraries. The biodiversity on Earth has the potential to introduce a nearly endless library of novel naturally derived therapeutic molecules, indicating that many promising findings have not been thoroughly examined [3].
