Pharmacognosy I Third Lecture 1 Introduction to Pharmacognosy

Pharmacognosy I – Third Lecture 1 - Introduction to Pharmacognosy MOHAMMED N. SABIR DECEMBER 2016

Pharmacognosy I – Third Lecture 1 - Introduction Some terms and abbreviations used during your study in pharmacognosy… - Natural Products (NPs) - Phytochemistry - Primary Metabolites - Secondary Metabolites - Biotechnology - Building blocks - Crude drugs - Quality Control (QC) 12/25/2021 2

Pharmacognosy I – Third Lecture 1 - Introduction Aims of the course - Descriptive study of selected medicinal plants - Highlight the role of Natural Products (NPs) in medicine - The biosynthetic pathways of NPs 12/25/2021 3

Pharmacognosy I – Third Lecture 1 - Introduction Aims of the course - Studying Crude drugs - Methods for isolation of NPs from crude materials (physicochemical investigation) 12/25/2021 4

Pharmacognosy I – Third Lecture 1 - Introduction Course objectives o Understand crude drugs, its classification and factors affect its storage and quality control. o A good understanding of the extraction, separation and isolation of natural products including chromatographic methods. 12/25/2021 5

Pharmacognosy I – Third Lecture 1 - Introduction Course objectives o Understand secondary metabolic pathways and its necessity in the production of their metabolites. o Know the mechanisms underlying the biochemical reactions that take place in secondary metabolism. 12/25/2021 6

Pharmacognosy I – Third Lecture 1 - Introduction Course objectives o Be able to categorize and recognize the classes of natural products. o Have enough information on the medicinal uses, mechanism of action, toxicities and the chemistry of the studied topics. 12/25/2021 7

Pharmacognosy I – Third Lecture 1 - Introduction Course contents - Introduction - Value of NPs - Physicochemical investigation for NPs - Secondary metabolism - General biosynthetic pathways for secondary metabolism 12/25/2021 8

Pharmacognosy I – Third Lecture 1 - Introduction Course contents - Drug discovery - Glycosides - Terpenoids - Steroids and steroid biosynthesis inhibitors - Polyphenolics (tannins, flavonoids and lignans) - Coumarins and chromones 12/25/2021 9

Pharmacognosy I – Third Lecture 1 - Introduction Reading List and References Journals and reviews (internet) 1. James E. Robbers, 1. Dewick P. M. , (1998). 1. Botanical Medicine in Marilyn K. Speedie, Medicinal Natural Products a Clinical Practice. A Varro E. Tyler, (1996). Biosynthetic Approach. First collection of newly Pharmacognosy and edition, Springer, India. approved literatures. Pharmacobiotechnolog (2008). Edited by y. First edition, Williams Ronald R. Watson, and Wilkins a Waverly Victor R. Preedy. company. Arizona Cancer Centre, University of Arizona, USA. Department of Nutrition and Diabetics, king's College London, UK. Key references 12/25/2021 Useful references 10

Pharmacognosy I – Third Key references Lecture 1 - Introduction Journals and reviews (internet) 2. Trease and Evans 2. Bhat S. V. , Nagasampagi B. A. , 2. Otto Sticher. (2008). W. Charles, and Sivakumar M. , (2007). Natural product Pharmacognosy, (2002). Chemistry of Natural Products. isolation. Natural Fifteenth edition. W. B. First edition. Springer, Narosa. Product Reports, Saunders Edinburgh India. London, New York, Philadelphia, St Louis, Sydney, Toronto. 12/25/2021 Useful references 11

Pharmacognosy I – Third Lecture 1 - Introduction 3. Saxena P. B. (2007). 3. Cannell J. P. Richard, (1998). Chemistry of Alkaloids. Natural Products Isolation. First edition. Discovery First edition, Glaxo Wellcome Publishing House. Research & Development, Stevenage, Herts, UK. Humana Press, Totowa New Jersey. 4. Robert K. Murray, Daryl 4. Eberhard Teuscher, (2006). K. Granner, Peter A. Medicinal Spices, A Handbook Mayes, Victor W. of Culinary Herbs, Spices, Rodwell. (2003). Spice Mixtures. First edition. Harper's Illustrated Medpharm Scientific Biochemistry. Twenty publishers Stuttgart. sixth edition. Mc Graw Hill. 5. Joule J. A. , and Mills K. (2002). Heterocyclic Chemistry. Fourth edition. Blackwell Science. 12/25/2021 12

Pharmacognosy I – Third Lecture 1 - Introduction 5. Chevallei A. (2005). 6. Chaudhuri Debabrata, Kar D. Alternative Medicine, Kumar, and Halder Soma. Treatment by Herbal (2008). A Handbook of Plant Products and Medicinal Biosynthetic Pathways. First Plants. First edition. NCBA. International Academia. 7. James R. Hanson, Natural Products. (2003). The secondary Metabolites. The Royal Society of Chemistry, Cambridge, UK 12/25/2021 13

Pharmacognosy I – Third Lecture 1 - Introduction 6. Bertram G. Katzung, 8. Pretsch E. , Buhlmann P. , and Anthony J. Trevor, Susan Affolter C. (2000). Structure B. Masters. Basic and determination of organic Clinical pharmacology compounds. First edition. (2009), by 11 th edition, Springer. Mc. Graw-Hill 9. Satyajit D. Sarker, Zahid Latif, and Alexander I. Gray (2006), Natural Products Isolation, SECOND EDITION, Humana Press, Totowa New Jersey 12/25/2021 10. Allen M. Schoffstall, Barbara A. Gaddis, and Melvin L. Druelinger. (2004). Microscale and Miniscale Organic Chemistry Laboratory Experiments. 2 nd Edition. Mc. Graw Hill, New York 14

Pharmacognosy I – Third Lecture 1 - Introduction Further readings… 12/25/2021 15

Pharmacognosy I – Third Lecture 1 - Introduction Further readings… 12/25/2021 16

Pharmacognosy I – Third Lecture 1 - Introduction Further readings… 12/25/2021 17

Pharmacognosy I – Third Lecture 1 - Introduction Further readings… 12/25/2021 18

Pharmacognosy I – Third 12/25/2021 Lecture 1 - Introduction 19

Pharmacognosy I – Third Lecture 1 - Introduction Course overview The course provides the fundamental information on pharmacognosy as a leading subject to understand drug-derived from natural sources including important biologically active medicines like: terpenoids, glycosides, volatile oils, tannins, steroids, flavonoids, and coumarins. 12/25/2021 20

Pharmacognosy I – Third Lecture 1 - Introduction The course also studies the origin of these natural products, the processes used for their extraction, separation, isolation and characterization as well as the biosynthetic routes that lead for the formation of these natural products. 12/25/2021 21

Pharmacognosy I – Third Lecture 1 - Introduction The biologic activities of these agents are discussed including their mechanism of action, clinical uses, toxicities, and the active constituents that are responsible for the biologic action. 12/25/2021 22

Pharmacognosy I – Third Lecture 1 - Introduction Structural modifications to produce semisynthetic products are also discussed if any. 12/25/2021 23

Pharmacognosy I – Third Lecture 1 - Introduction Lecture overview • Definition • Historical Aspects • Disciplines to understand pharmacognosy • Development of medicinal chemistry • Value of natural products 12/25/2021 24

Pharmacognosy I – Third Lecture 1 - Introduction Lecture overview • Examples • Crude drug and classification systems • Physicochemical investigation of natural products • Summary & conclusion 12/25/2021 25

Pharmacognosy I – Third Lecture 1 - Introduction to Pharmacognosy… Pharmacognosy studies all aspects of medications (drugs) derived form natural sources including (Plants, Micro Organisms, Marine products, Insects and Animals). 12/25/2021 26

Pharmacognosy I – Third Lecture 1 - Introduction to Pharmacognosy… It also concerns the biochemical pathways that are involved in the biosynthesis of these drugs (drug discovery). 12/25/2021 27

Pharmacognosy I – Third Lecture 1 - Introduction to Pharmacognosy… and the techniques involved for their isolation from the crude materials (Isolation) 12/25/2021 28

Pharmacognosy I – Third Lecture 1 - Introduction to Pharmacognosy… The chemical modification to approach more effective and less toxic product and their pharmacological properties (drug design). 12/25/2021 29

Pharmacognosy I – Third Lecture 1 - Introduction to Pharmacognosy… All the physical and chemical characterizations of these agents as well (Identification). 12/25/2021 30

Pharmacognosy I – Third Lecture 1 - Introduction to Pharmacognosy… So… In addition to studying drugs derived from NPs, 12/25/2021 31

Pharmacognosy I – Third Lecture 1 - Introduction to Pharmacognosy… It is a drug discovery involving; isolation, drug design and identification techniques. 12/25/2021 32

Pharmacognosy I – Third Lecture 1 - Introduction Biotechnology [recombinant DNA technology (r. DNA)], has opened new perspectives in pharmacognosy… 12/25/2021 33

Pharmacognosy I – Third Lecture 1 - Introduction This is achieved through production of chemical entities or drugs by tissue cultures via genetic engineering (this needs a good understanding of enzymology). 12/25/2021 34

Pharmacognosy I – Third Lecture 1 - Introduction Biotechnology is applied to: 1 - Increase the yield of the drug As in Taxol (an anticancer agent). 12/25/2021 35

Pharmacognosy I – Third Lecture 1 - Introduction 2 - Modification on the secondary metabolite through genetic engineering to obtain less toxic and more effective drug as well as enhance drug delivery (ex: Antibiotics, antivirals and anticancers). 12/25/2021 36

Pharmacognosy I – Third Lecture 1 - Introduction 3 - It also provide methods for production of many drugs that cannot be synthesized by chemical synthesis: - 12/25/2021 37

Pharmacognosy I – Third Lecture 1 - Introduction - Insulin form E. coli. - Tissue plasminogen activator [t-PA] from melanoma cell lines. - Human serum albumin (HSA) from E. coli. 12/25/2021 38

Pharmacognosy I – Third Lecture 1 - Introduction - Development of vaccines: a) Separation of a pure antigen using a specific monoclonal antibody. b) Synthesis of an antigen with the help of a cloned gene. c) Synthesis of peptides to be used as vaccines. 12/25/2021 39

Pharmacognosy I – Third Lecture 1 - Introduction Biotechnology and drug discovery… 12/25/2021 40

Pharmacognosy I – Third Lecture 1 - Introduction Cell and tissue culture can be obtained from many plant species, M. Os. , animals or human. 12/25/2021 41

Pharmacognosy I – Third Lecture 1 - Introduction In such In vitro culture, each cell has all the genes necessary for all the functions of a living organism, including secondary metabolism. 12/25/2021 42

Pharmacognosy I – Third 12/25/2021 Lecture 1 - Introduction 43

Pharmacognosy I – Third 12/25/2021 Lecture 1 - Introduction 44

Pharmacognosy I – Third KS: ketosynthase MAT: malonyl-acetyl transferase DH: dehydratase KR: ketoreductase ACP: acyl carrier protein Lecture 1 - Introduction The biosynthetic pathway for the fungal polyketide 6 methylsalicylic acid (6 MSA). 6 -MSA is assembled from four ketide units (one acetate and three malonates). Extension, carrying out different levels of reductive processing at each stage. (Staunton and Weismann, Nat. Prod. Rep. , 2001, 18, 380– 416) 12/25/2021 45

Pharmacognosy I – Third Lecture 1 - Introduction KS: ketoacyl synthase AT: acyl transferase DH: dehydratase ER: enoyl reductase ACP: acyl carrying protein 12/25/2021 46

Pharmacognosy I – Third Lecture 1 - Introduction Historical aspects -Papyrus Ebersc (1600 B. C. ) 12/25/2021 47

Pharmacognosy I – Third Lecture 1 - Introduction -Greek pharmaco-botanist in the first century A. D. (Pedanios Dioscorides) and “materia medica” 12/25/2021 48

Pharmacognosy I – Third Lecture 1 - Introduction -Li Shih Chen and published in 1596 A. D. , listed more than 2000 drugs of natural origin. About 5000 native medicinal herbs are used in China today 12/25/2021 49

Pharmacognosy I – Third Lecture 1 - Introduction -A collection of hymns predating 1000 B. C. , included more than 1000 healing herbs, many of which continue to be used in Ayurvedic medicine (Hindu traditional medicine). 12/25/2021 50

Pharmacognosy I – Third Lecture 1 - Introduction The Unani (Islamic Medicine) has contribution in this field by (Avicenna 890 -1037 A. D. ), he collected his knowledge about medicinal plants in the Kitab-Al. Shifa’a. 12/25/2021 51

Pharmacognosy I – Third Lecture 1 - Introduction The word Pharmacognosy formed from two Greek words pharmakon (drug) and gnosis (knowledge), this title was introduced by C. A. Seydler, a German medical student, who used Analytica pharmacognostica for his dissertation in 1815. 12/25/2021 52

Pharmacognosy I – Third Lecture 1 - Introduction However, recent historical research has found an earlier usage of “Pharmacognosis”. J. A. Schmidt used that title in his Lehrbuch der Materia medica, published in Vienna in 1811, to describe the study of medicinal plants and their properties. 12/25/2021 53

Pharmacognosy I – Third Lecture 1 - Introduction A complete understanding of medicinal plants involves a number of disciplines including: 1. Commerce. 2. Botany. 3. Horticulture. 4. Chemistry. 5. Enzymology. 6. Genetics. 7. Quality control. 8. Pharmacology. 12/25/2021 54

Pharmacognosy I – Third Lecture 1 - Introduction The use of modern isolation techniques and pharmacological testing procedures means that new plant drugs usually fined their way into medicine as purified substances rather than in the form of galenical preparations. 12/25/2021 55

Pharmacognosy I – Third Lecture 1 - Introduction Advances in synthetic chemistry and production of drugs with more complicated chemical structure has opened a new field which is known as Pharmaceutical and Medicinal Chemistry 12/25/2021 56

Pharmacognosy I – Third Lecture 1 - Introduction 1. Pharmacology; studying drug actions and effects. 2. Medicinal Chemistry; the studying the chemical aspects of drugs, their design, synthesis and mechanism of actions on molecular level. 3. Pharmacognosy; dealing with medicines derived from natural sources. 12/25/2021 57

Pharmacognosy I – Third Lecture 1 - Introduction Pharmacognosy Drug Pharmacology 12/25/2021 Pharmaceutical and Medicinal Chemistry 58

Pharmacognosy I – Third Lecture 1 - Introduction Value of natural drugs products Role of compounds that are derived from natural sources could be summarized as follows: - 12/25/2021 59

Pharmacognosy I – Third Lecture 1 - Introduction Value of natural drugs products • They provide a number of extremely useful drugs that are difficult, if not impossible, to be produced commercially by synthetic means, like: 12/25/2021 60

Pharmacognosy I – Third Lecture 1 - Introduction alkaloids of opium poppy, ergot, and Solanaceous plants; the cardiotonic glycosides of digitalis; most of the antibiotics; and all of the serums, vaccines, and related products. 12/25/2021 61

Pharmacognosy I – Third Lecture 1 - Introduction • Natural sources also supply basic compounds (templates) that may be modified slightly to render them more effective or less toxic. 12/25/2021 62

Pharmacognosy I – Third Lecture 1 - Introduction Examples: The modification of morphine molecule to codeine, and modification of podophyllotoxin to teniposide. 12/25/2021 63

Pharmacognosy I – Third Lecture 1 - Introduction • The utility of natural products as (prototypes) or models for synthetic drugs possessing physiologic activities similar to the originals, 12/25/2021 64

Pharmacognosy I – Third Lecture 1 - Introduction Examples: -Procaine and similar local anesthetics. -Dicoumarol and other oral anticoagulant (warfarin). 12/25/2021 65

Pharmacognosy I – Third Lecture 1 - Introduction • As (precursors) of significant drugs; some natural products contain compounds that demonstrate little or no activity themselves but upon modification by chemical or biological means; they will be converted to potent drugs… 12/25/2021 66

Pharmacognosy I – Third Lecture 1 - Introduction But these agents are not easily obtained by other methods like: 12/25/2021 67

Pharmacognosy I – Third Lecture 1 - Introduction Taxol which may be synthesized from bactin III, which occur in the leaves of Pacific Yew. Whereas taxol it self is found only in the bark of scarce Pacific Yew. 12/25/2021 68

Pharmacognosy I – Third Bactin III 12/25/2021 Lecture 1 - Introduction Taxol 69

Pharmacognosy I – Third Lecture 1 - Introduction Below are examples of some drugs that are derived from natural sources, their semisynthetic and their prototypes 12/25/2021 70

Pharmacognosy I – Third Lecture 1 - Introduction Crude drugs Are NPs that has not been advanced in value or improved in condition by any process or treatment beyond that which is essential for its proper packing and prevention from deterioration. 12/25/2021 71

Pharmacognosy I – Third Lecture 1 - Introduction Classification of crude drugs 1. Alphabetical classification; 12/25/2021 72

Pharmacognosy I – Third Lecture 1 - Introduction Alphabetical classification Merits: • It is easy and quick to use • There is no repetition of entries and is devoid of confusion. • In this system location, tracing and addition of drug entries is easy. 12/25/2021 73

Pharmacognosy I – Third Lecture 1 - Introduction Alphabetical classification Demerits: There is no relationship between previous and successive drug entries. Examples: Acacia, Benzoin, Cinchona, Dill, Ergot, Fennel, Gentian, Hyoscyamus, Ipecacuanha, Jalap, Kurchi, Liquorice, Mints, Nuxvomica, Opium, Podophyllum, Quassia, Rauwolfia, Senna, Vasaka, Wool fat, Yellow bees wax, Zeodary. 12/25/2021 74

Pharmacognosy I – Third Lecture 1 - Introduction Classification of crude drugs 2. Morphological classification; - Organized (Solid) Wood, leaves, bark…etc. - Non-organized (Liquid) Waxes, gums, resins, etc. 12/25/2021 75

Pharmacognosy I – Third Lecture 1 - Introduction Unorganized Drugs. Dried latex– Opium, Papain Dried Juice– Aloe, Kino Dried extracts– Agar, Alginate, Black catechu, Pale catechu, Pectin, Waxes - Beeswax, Spermaceti, Carnauba wax Gums – Acacia, Guar Gum, Indian Gum, Sterculia, Tragacenth. Resins– Asafoetida, Benzoin, Colophony, copaiba Guaiacum, Guggul, Mastic, Coal tar, Tolu balsam, Storax, Sandarac. 12/25/2021 76

Pharmacognosy I – Third Lecture 1 - Introduction Unorganized Drugs. Volatile oil– Turpentine, Anise, Coriander, Peppermint, Rosemary, Sandalwood, Cinnamon, Lemon, Caraway, Dill, Clove, Eucalyptus, Nutmeg, Camphor. Fixed oils and Fats– Arachis, Castor, Chalmoogra, Coconut, Cotton seed, Linseed, Olive, Sesame, Almond, Theobroma, Cod-liver, Halibut liver, Kokum butter. Animal Products – Bees wax, Cantharides, Cod-liver oil, Gelatin, Halibut liver oil, Honey, Shark liver oil, shellac, Spermaceti wax, wool fat, musk, Lactose. Fossil organism and Minerals– Bentonite, Kaolin, Kiesslguhr, Talc. 12/25/2021 77

Pharmacognosy I – Third Lecture 1 - Introduction Classification of crude drugs 3. Taxonomic classification; - More advanced 12/25/2021 78

Pharmacognosy I – Third Lecture 1 - Introduction Taxonomic classification Plant Kingdom Thallophyta Pteridophyta Gymnosperm Angiosperm Phyllum 12/25/2021 Order Family Drugs 79

Pharmacognosy I – Third Lecture 1 - Introduction Classification of crude drugs 4. Pharmacological classification; - Advanced, depends on biological actions of the plant. 12/25/2021 80

Pharmacognosy I – Third Lecture 1 - Introduction Pharmacological Classification of Drugs based on Pharmacological action Pharmacological Action Anticancer Anti-inflammatory Antiamoebic Antiasthmatic Anthelminthic Antispasmodic Astringent Analgesic Bitter tonic Carminatives Purgatives Expectorant Cardiotonic Tranquilizers 12/25/2021 Drug Vinca, Podophyllum, Taxus Colchicum, Turmeric Ipecac root, Kurchi bark Ephedra, Lobelia Male fern, Quassia wood Datura, Hyoscyamus Catechu Opium, poppy Quassia wood, Nux-vomica, Gentian Coriander, fennel, clove, peppermint Senna, Rhubarb Tulsi, Balsam of Tolu, Vasaka Digitalis, Squill, Strophanthus Rauwolfia Roots 81

Pharmacognosy I – Third Lecture 1 - Introduction Classification of crude drugs 5. Chemical classification; - 12/25/2021 Doesn’t show species or genus. 82

Pharmacognosy I – Third Lecture 1 - Introduction Chemical Classification Carbohydrates Glycosides Tannins Volatile oils and Terpenoids Lipids Resins Alkaloids Proteins Vitamins 12/25/2021 83

Pharmacognosy I – Third Lecture 1 - Introduction Classification of crude drugs 6. Chemotaxonomic classification; - Needs a lot of time to recognize the plant, it depends on taxa and secondary metabolites. 12/25/2021 84

Pharmacognosy I – Third Lecture 1 - Introduction Chemotaxonomic Classification This system of classification relies on the chemical similarity of a taxon i. e. it is based on the existence of relationship between constituents in various plants. 12/25/2021 85

Pharmacognosy I – Third Lecture 1 - Introduction Classification of crude drugs Taxonomic classification is more applied, since it depends on the genetics and morphological features of the plant. 12/25/2021 86

Pharmacognosy I – Third Lecture 1 - Introduction Secondary metabolism and natural products - Secondary metabolites and building blocks… - Natural products (NPs) and their chemistry… - Importance of NPs in modern medicine…

Pharmacognosy I – Third Lecture 1 - Introduction Secondary metabolism and natural products - The scope of pharmacognosy in modern medicine… 12/25/2021 88

Pharmacognosy I – Third Lecture 1 - Introduction Natural products in drug discovery… 12/25/2021 89

Pharmacognosy I – Third Lecture 1 - Introduction - Lecture review… - Next lecture topics… 12/25/2021 90

Pharmacognosy I – Third Lecture 1 - Introduction Thank You 12/25/2021 91