Introduction to Pharmacognosy Pharmacognosy I – Third Lecture 1- Introduction Mohammed N. Sabir December 2016 Introduction to Pharmacognosy

Some terms and abbreviations used during your study in pharmacognosy… 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) 9/19/2018

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 9/19/2018

(physicochemical investigation) Pharmacognosy I – Third Lecture 1- Introduction Aims of the course - Studying Crude drugs - Methods for isolation of NPs from crude materials (physicochemical investigation) 9/19/2018

Pharmacognosy I – Third Lecture 1- Introduction Course objectives   Understand crude drugs, its classification and factors affect its storage and quality control. A good understanding of the extraction, separation and isolation of natural products including chromatographic methods. 9/19/2018

Pharmacognosy I – Third Lecture 1- Introduction Course objectives   Understand secondary metabolic pathways and its necessity in the production of their metabolites. Know the mechanisms underlying the biochemical reactions that take place in secondary metabolism. 9/19/2018

Be able to categorize and recognize the classes of natural products. Pharmacognosy I – Third Lecture 1- Introduction Course objectives Be able to categorize and recognize the classes of natural products. Have enough information on the medicinal uses, mechanism of action, toxicities and the chemistry of the studied topics. 9/19/2018

Pharmacognosy I – Third Lecture 1- Introduction Course contents - Introduction - Value of NPs - Physicochemical investigation for NPs - Secondary metabolism - General biosynthetic pathways for secondary metabolism 9/19/2018

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 9/19/2018

Journals and reviews (internet) Pharmacognosy I – Third Lecture 1- Introduction Reading List and References‌ Key references Useful references Journals and reviews (internet) 1. James E. Robbers, Marilyn K. Speedie, Varro E. Tyler, (1996). Pharmacognosy and Pharmacobiotechnology. First edition, Williams and Wilkins a Waverly company. 1. Dewick P. M., (1998). Medicinal Natural Products a Biosynthetic Approach. First edition, Springer, India. 1. Botanical Medicine in Clinical Practice. A collection of newly approved literatures. (2008). Edited by Ronald R. Watson, Victor R. Preedy. Arizona Cancer Centre, University of Arizona, USA. Department of Nutrition and Diabetics, king's College London, UK. 9/19/2018

Journals and reviews (internet) Pharmacognosy I – Third Lecture 1- Introduction Key references 2. Trease and Evans W. Charles, Pharmacognosy, (2002). Fifteenth edition. W.B. Saunders Edinburgh London, New York, Philadelphia, St Louis, Sydney, Toronto. Useful references 2. Bhat S.V., Nagasampagi B. A., and Sivakumar M., (2007). Chemistry of Natural Products. First edition. Springer, Narosa. India. Journals and reviews (internet) 2. Otto Sticher. (2008). Natural product isolation. Natural Product Reports, 9/19/2018

Pharmacognosy I – Third Lecture 1- Introduction 3. Saxena P.B. (2007). Chemistry of Alkaloids. First edition. Discovery Publishing House. 3. Cannell J. P. Richard, (1998). Natural Products Isolation. First edition, Glaxo Wellcome Research & Development, Stevenage, Herts, UK. Humana Press, Totowa New Jersey.   Robert K. Murray, Daryl K. Granner, Peter A. Mayes, Victor W. Rodwell. (2003). Harper's Illustrated Biochemistry. Twenty sixth edition. Mc Graw Hill. 4. Eberhard Teuscher, (2006). Medicinal Spices, A Handbook of Culinary Herbs, Spices, Spice Mixtures. First edition. Medpharm Scientific publishers Stuttgart. 5. Joule J. A., and Mills K. (2002). Heterocyclic Chemistry. Fourth edition. Blackwell Science. 9/19/2018

Pharmacognosy I – Third Lecture 1- Introduction 5. Chevallei A. (2005). Alternative Medicine, Treatment by Herbal Products and Medicinal Plants. First edition. International Academia. 6. Chaudhuri Debabrata, Kar D. Kumar, and Halder Soma. (2008). A Handbook of Plant Biosynthetic Pathways. First edition. NCBA.   7. James R. Hanson, Natural Products. (2003) . The secondary Metabolites. The Royal Society of Chemistry, Cambridge, UK 9/19/2018

Pharmacognosy I – Third Lecture 1- Introduction 6. Bertram G. Katzung, Anthony J. Trevor, Susan B. Masters. Basic and Clinical pharmacology (2009), by 11th edition, McGraw-Hill 8. Pretsch E., Buhlmann P., and Affolter C. (2000). Structure determination of organic compounds. First edition. Springer.   9. Satyajit D. Sarker, Zahid Latif, and Alexander I. Gray (2006), Natural Products Isolation, SECOND EDITION, Humana Press, Totowa New Jersey 10. Allen M. Schoffstall, Barbara A. Gaddis, and Melvin L. Druelinger. (2004). Microscale and Miniscale Organic Chemistry Laboratory Experiments. 2nd Edition. McGraw Hill, New York 9/19/2018

Further readings… Pharmacognosy I – Third Lecture 1- Introduction 9/19/2018

Further readings… Pharmacognosy I – Third Lecture 1- Introduction 9/19/2018

Further readings… Pharmacognosy I – Third Lecture 1- Introduction 9/19/2018

Further readings… Pharmacognosy I – Third Lecture 1- Introduction 9/19/2018

Pharmacognosy I – Third Lecture 1- Introduction 9/19/2018

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.  9/19/2018

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. 9/19/2018

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. 9/19/2018

Pharmacognosy I – Third Lecture 1- Introduction Structural modifications to produce semisynthetic products are also discussed if any. 9/19/2018

Disciplines to understand pharmacognosy Pharmacognosy I – Third Lecture 1- Introduction Lecture overview Definition Historical Aspects Disciplines to understand pharmacognosy Development of medicinal chemistry Value of natural products 9/19/2018

Crude drug and classification systems Pharmacognosy I – Third Lecture 1- Introduction Lecture overview Examples Crude drug and classification systems Physicochemical investigation of natural products Summary & conclusion 9/19/2018

Introduction to Pharmacognosy… Pharmacognosy I – Third Lecture 1- Introduction Introduction to Pharmacognosy… Pharmacognosy studies all aspects of medications (drugs) derived form natural sources including (Plants, Micro Organisms, Marine products, Insects and Animals). 9/19/2018

Introduction to Pharmacognosy… Pharmacognosy I – Third Lecture 1- Introduction Introduction to Pharmacognosy… It also concerns the biochemical pathways that are involved in the biosynthesis of these drugs (drug discovery). 9/19/2018

Introduction to Pharmacognosy… Pharmacognosy I – Third Lecture 1- Introduction Introduction to Pharmacognosy… and the techniques involved for their isolation from the crude materials (Isolation) 9/19/2018

Introduction to Pharmacognosy… Pharmacognosy I – Third Lecture 1- Introduction Introduction to Pharmacognosy… The chemical modification to approach more effective and less toxic product and their pharmacological properties (drug design). 9/19/2018

Introduction to Pharmacognosy… Pharmacognosy I – Third Lecture 1- Introduction Introduction to Pharmacognosy… All the physical and chemical characterizations of these agents as well (Identification). 9/19/2018

So… Introduction to Pharmacognosy… Pharmacognosy I – Third Lecture 1- Introduction Introduction to Pharmacognosy… So… In addition to studying drugs derived from NPs, 9/19/2018

Introduction to Pharmacognosy… Pharmacognosy I – Third Lecture 1- Introduction Introduction to Pharmacognosy… It is a drug discovery involving; isolation, drug design and identification techniques. 9/19/2018

Pharmacognosy I – Third Lecture 1- Introduction Biotechnology [recombinant DNA technology (rDNA)], has opened new perspectives in pharmacognosy… 9/19/2018

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). 9/19/2018

Biotechnology is applied to:- 1- Increase the yield of the drug Pharmacognosy I – Third Lecture 1- Introduction Biotechnology is applied to:- 1- Increase the yield of the drug As in Taxol (an anticancer agent). 9/19/2018

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). 9/19/2018

Pharmacognosy I – Third Lecture 1- Introduction 3- It also provide methods for production of many drugs that cannot be synthesized by chemical synthesis:- 9/19/2018

Tissue plasminogen activator [t-PA] from melanoma cell lines. 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. 9/19/2018

- Development of vaccines: Pharmacognosy I – Third Lecture 1- Introduction - Development of vaccines: 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. 9/19/2018

Biotechnology and drug discovery… Pharmacognosy I – Third Lecture 1- Introduction Biotechnology and drug discovery… 9/19/2018

Pharmacognosy I – Third Lecture 1- Introduction Cell and tissue culture can be obtained from many plant species, M.Os., animals or human. 9/19/2018

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. 9/19/2018

Pharmacognosy I – Third Lecture 1- Introduction 9/19/2018

Pharmacognosy I – Third Lecture 1- Introduction 9/19/2018

Pharmacognosy I – Third Lecture 1- Introduction KS: ketosynthase MAT: malonyl-acetyl transferase DH: dehydratase KR: ketoreductase ACP: acyl carrier protein 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) 9/19/2018

ACP: acyl carrying protein Pharmacognosy I – Third Lecture 1- Introduction KS: ketoacyl synthase AT: acyl transferase DH: dehydratase ER: enoyl reductase ACP: acyl carrying protein 9/19/2018

Historical aspects -Papyrus Ebersc (1600 B.C.) Pharmacognosy I – Third Lecture 1- Introduction Historical aspects -Papyrus Ebersc (1600 B.C.) 9/19/2018

Pharmacognosy I – Third Lecture 1- Introduction -Greek pharmaco-botanist in the first century A.D. (Pedanios Dioscorides) and “materia medica” 9/19/2018

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 9/19/2018

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). 9/19/2018

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. 9/19/2018

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. 9/19/2018

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. 9/19/2018

Pharmacognosy I – Third Lecture 1- Introduction A complete understanding of medicinal plants involves a number of disciplines including:- Commerce. Botany. Horticulture. Chemistry. Enzymology. Genetics. Quality control. Pharmacology. 9/19/2018

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. 9/19/2018

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 9/19/2018

Pharmacology; studying drug actions and effects. Pharmacognosy I – Third Lecture 1- Introduction Pharmacology; studying drug actions and effects. Medicinal Chemistry; the studying the chemical aspects of drugs, their design, synthesis and mechanism of actions on molecular level. Pharmacognosy; dealing with medicines derived from natural sources. 9/19/2018

Pharmaceutical and Medicinal Chemistry Pharmacognosy I – Third Lecture 1- Introduction Drug Pharmacognosy Pharmaceutical and Medicinal Chemistry Pharmacology 9/19/2018

Value of natural drugs products 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:- 9/19/2018

Value of natural drugs products 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: 9/19/2018

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. 9/19/2018

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. 9/19/2018

Pharmacognosy I – Third Lecture 1- Introduction Examples:- The modification of morphine molecule to codeine, and modification of podophyllotoxin to teniposide. 9/19/2018

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, 9/19/2018

-Procaine and similar local anesthetics. Pharmacognosy I – Third Lecture 1- Introduction Examples:- -Procaine and similar local anesthetics. -Dicoumarol and other oral anticoagulant (warfarin). 9/19/2018

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… 9/19/2018

But these agents are not easily obtained by other methods like: Pharmacognosy I – Third Lecture 1- Introduction But these agents are not easily obtained by other methods like: 9/19/2018

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. 9/19/2018

Bactin III Taxol Pharmacognosy I – Third Lecture 1- Introduction 9/19/2018

Pharmacognosy I – Third Lecture 1- Introduction Below are examples of some drugs that are derived from natural sources, their semisynthetic and their prototypes 9/19/2018 (Fig. 1)

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. 9/19/2018

Classification of crude drugs 1. Alphabetical classification; Pharmacognosy I – Third Lecture 1- Introduction Classification of crude drugs 1. Alphabetical classification; 9/19/2018

Alphabetical classification 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. 9/19/2018

Alphabetical classification Pharmacognosy I – Third Lecture 1- Introduction 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. Alphabetical classification 9/19/2018

Classification of crude drugs 2. Morphological classification; 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. 9/19/2018

Unorganized Drugs. Dried latex– Opium, Papain Dried Juice– Aloe, Kino 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, Tar, Tolu balsam, Storax, Sandarac. 9/19/2018

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. 9/19/2018

Classification of crude drugs 3. Taxonomic classification; Pharmacognosy I – Third Lecture 1- Introduction Classification of crude drugs 3. Taxonomic classification; - More advanced 9/19/2018

Taxonomic classification Pharmacognosy I – Third Lecture 1- Introduction Taxonomic classification Plant Kingdom Thallophyta Pteridophyta Gymnosperm Angiosperm Phyllum Order Family Drugs 9/19/2018

Classification of crude drugs Pharmacognosy I – Third Lecture 1- Introduction Classification of crude drugs 4. Pharmacological classification; - Advanced, depends on biological actions of the plant. 9/19/2018

Pharmacological Classification Pharmacognosy I – Third Lecture 1- Introduction Pharmacological Classification Classification of Drugs based on Pharmacological action Pharmacological Action Drug Anticancer Anti-inflammatory Antiamoebic Antiasthmatic Anthelminthic Antispasmodic Astringent Analgesic Bitter tonic Carminatives Purgatives Expectorant Cardiotonic Tranquilizers 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 9/19/2018

Classification of crude drugs Pharmacognosy I – Third Lecture 1- Introduction Classification of crude drugs 5. Chemical classification; - Doesn’t show species or genus. 9/19/2018

Chemical Classification Pharmacognosy I – Third Lecture 1- Introduction Chemical Classification Carbohydrates Glycosides Tannins Volatile oils and Terpenoids Lipids Resins Alkaloids Proteins Vitamins 9/19/2018

Classification of crude drugs 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. 9/19/2018

Chemotaxonomic Classification 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. 9/19/2018

Classification of crude drugs 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. 9/19/2018

Secondary metabolism and natural products 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… 9/19/2018

Secondary metabolism and natural products Pharmacognosy I – Third Lecture 1- Introduction Secondary metabolism and natural products - The scope of pharmacognosy in modern medicine… 9/19/2018

Natural products in drug discovery… Pharmacognosy I – Third Lecture 1- Introduction Natural products in drug discovery… 9/19/2018

- Lecture review… - Next lecture topics… Pharmacognosy I – Third Lecture 1- Introduction - Lecture review… - Next lecture topics… 9/19/2018

Pharmacognosy I – Third Lecture 1- Introduction Thank You 9/19/2018