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What Is Pharmaceutical Biology? • Applied Science Dealing with Living

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College 1/1 - 1 What is Pharmaceutical Biology? • Applied science dealing with living cells as host or producer of natural products with pharamcological activitiy – Naturally origin in living organisms – biosynthesis – Biological activity and application – Improving production processes College 1/1 - 2 Goal of this lecture series • Nature as source for gene and drug discovery • Biodiversity / Chemodiversity • Synthetic Biology, Metabolic Engineering • Drug regulation • Economic value College 1/1 - 3 Areas of Pharmaceutical Biology Microbiology Botanica •Bakteria • Taxonomy • Fungi • Systematics • Marine organisms • Ethnobotanics Pharmaceutical Biology Fytotherapy Bioanalytics • Phytopharmacology • High Throughput Screening • Toxikology • Natural Product Chemistry • Regulation of herbal • Standardisation medicinal drugs College 1/1 - 4 Natural Products in practise From professional use to self medication College 1/1 - 5 Nature is most important source for new drugs and therapeutic agents College 1/1 - 6 Natural Products • From microorganisms – Streptomyces – Penicillium • From plants – Veele medicinale planten • From animals – Corals – Marine organisms College 1/1 - 7 Secondary natural products from plants in pharmacy • Pure isolated compounds – morfine, digoxine, kinine, vinblastine, paclitaxel • Semi-synthetics – podofyllotoxine → etoposide – artemisinine → arteether • Synthetics (natural product is ‘template’) – E.g. atropine, morfine, cocaïne, tubocurarine College 1/1 - 8 Plant like drugs • Oldest form of pharmacotherapy • Since 19th century isolation of natural productions • Source for new drugs: chemical compounds from plants and their derivatives • Fytotherapeutics • Homeopathic medicines College 1/1 - 9 History Historic roots of traditional medicine College 1/1 - 10 History • Starch tablets from Mesopotamia (from 2500 b.c.) College 1/1 - 11 College 1/1 - 12 History Theophrastus (300 b.c.) studied medicinal plants and is called father of botany College 1/1 - 13 History Dioscorides Father of pharmaceutical biology and pharmacy Writer of Materia Medica. Up to the 16th century a standard text book College 1/1 - 14 Hildegard von Bingen, 1098-1179 • Kloster medicine • Liber Simplicis Medicinae • Liber Compositae Medicinae – 280 plants described – Translation from Latin to German – First scientific use of plants College 1/1 - 15 Klostermedicine • No topic for medicine at universities • First kloster founded 527 by Benedikt von Nursia • Early and late middel age • Medical nursery in Europe • Based on plants • Place of first medical libary • Bartolomaeus Anglicus (De proprietatibus rerum ) • Thomas Cantimpratensis • Vinzenz von Beauvais (Speculum maius) • Albertus Magnus • Konrad von Megenberg (Buch von den natürlichen Dingen ) College 1/1 - 16 Avicenna, 979-1037 Abu Ali al-Husain ibn Sina-e Balkhi • Persian medicus • Author of 200 books – al-Shifa (the book of healing) – Al-Qanun fi-l-Tibb (The canon of healing) • Eastern fytotherapie – Based on tradition of Aristoteles College 1/1 - 17 From history to presence • Plants are essential for pharmacy •Examples: – Papaver somniferum – Podophyllum hexandrum – Artemisia annua College 1/1 - 18 From history to presence • 40% of clinically used drugs are derived from nature O N N Natural Product Syntheticum O N N Caffeine Sildenafil caffeine Furanocoumarine Chromoglycinzuur O N O HN N Morfine Methadon, Pethidine N Dicoumarine Warfarine O S O N Sildenafil Artemisinine Artemether N College 1/1 - 19 Microorganisms as source for drug discovery get more and more important • Actinomycetes (Streptomycetes) 60% • Bacillaceae • Pseudomonaceae • Myxobacteria •Enterobacteria • Fungi imperfecti 1% only of microorganisms are known! • Penicillium • Aspergillus • Acremonium • Basidomycetes College 1/1 - 20 Natural Products from microorganisms O S H3C • Penicillin H3C OH N H C H C 3 CH •Streptomycine O 3 3 CH3 O OH O HO O NHCH Cl NH 3 Epothilone OH O O NH OO OH HO N O NH O O H O 2 O O O Cl HN O O H O O N N N N HO N H NH O O O O 2 N OH O HO OH OH N O N O H N H N H N N N O H O OH O O Cyclosporin C Vancomycine College 1/1 - 21 Biodiversity • What is Biodiversity? Divergence of life College 1/1 - 22 Biodiversity • Complex and high number of animals, plants and microorganisms • Extraordinary high number of varieties College 1/1 - 23 Biodiversity • All organisms produce a different pattern of natural products Chemodiversity College 1/1 - 24 The beginning of wisdom is to give a Botany name to the unkwon TAXONOMY College 1/1 - 25 Botany Carl von Linnee (Linneaus) - Classification of nture according to common distinguishing marks -Scientific nomenclature - e.g. Papaver somniferum L. College 1/1 - 26 Botany / Evolution Charles Darwin Founder the evolution theory. College 1/1 - 27 Botany / Evolution Giving a name based on relationships. Possible through: -Evolution -taxonomy -DNA sequencing Phylogenicity College 1/1 - 28 Genetic origin of Chardonnay wine Synonyms Pinot Chardonnay, Beaunois, Morillon, Weißer Clevner and Feinburgunder Chardonnay-grapes (Vitis vinifera) Phylogenetic origin of Chardonnay wine Locus VVMD5 Locus VVMD28 Results: - Pinot noir: known by Romans - Gouais blanc: Origin in East Europe - both well known in the middle age - natural crossing of Pinot and Gouais Blanc (P) Pinot noir, (G) Gouais blanc, (1) Aligoté, (2) Aubin vert, (3) Auxerrois, (4) Bachet noir, (5) Beaunoir, (6) Chardonnay, (7) Franc noir de la Haute Saône, (8) Gamay blanc Gloriod, (9) Gamay noir, (10) Knipperlé, (11) Melon, (12) Peurion, (13) Romorantin, (14) Roublot, (15) Sacy, (P) Pinot noir und (G) Gouais blanc Bowers, J. (1999) Science, 285:1562 Chemodiversity • Chemodiversity is the source for drug discovery • But, how to find? •High Through Put Analytics (HTPA) •High Through Put Screening (HTPS) We see later in the next chapter ! College 1/1 - 31 Ethnopharmacy • Ethnobotany = traditional use of plants • Ethnofarmacie = traditional use medicine / healing techniques J. W. Harshberger 1869-1929 College 1/1 - 32 Ethnobotany - Ethnopharmacy Homeopathie, Kneipp, Bach TCM Kampo Traditionele Noordamerikanse Ayuverda Geneeskunde Jamu Traditionele Traditionele Afrikanse Zuidamerikanse Geneeskunde Geneeskunde College 1/1 - 33 College 1/1 - 34 Ethnobotany - Ethnofarmacy College 1/1 - 35 Natural drugs? Is it possible to have ? What is the most apperent way of treating sick people in the world? College 1/1 - 36 That´s it! College 1/1 - 37 Contrasts between 1st and 3rd world… College 1/1 - 38 Natural drugs? • Most people in the world are dependend on plants and herbal medicinal products • More and more interest in traditional medicine in so called western world • “Back to Nature” trend in industrial communities College 1/1 - 39 Eisenberg, D. M. et al. JAMA 1998;280:1569-1575. Eisenberg, D. M. et al. JAMA 1998;280:1569-1575. Natural drugs? • More of: –Fytotherapy –Homeopathy – Traditional art of healing • More than 120 therapies are already accepted! College 1/1 - 42 Use of medicinal plants • Ca. 80% of world population is depended on. • Synthetic drugs mostly too expensive • Highly depended on culturl background • WHO considers herbal medicinal products as essential part in the arsenal of medicines used today College 1/1 - 43 Active constitutens • Some plants are well characterised, but mostly we do not much about constituents • Plants may contain a toxic principle that is accepted as wanted active drug • Synthetic drugs as single preparations are preferred College 1/1 - 44 Ethnobotany - Ethnofarmacy • Transfer from traditional medicine to clinically drugs works: • Artemisinine - Anti-malaria • Podofyllotoxine - Anti-cancer • Paclitaxel -Anti-cancer College 1/1 - 45.
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