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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

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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

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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

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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

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History Historic roots of traditional medicine

College 1/1 - 10 History

• Starch tablets from Mesopotamia (from 2500 b.c.)

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College 1/1 - 12 History

Theophrastus (300 b.c.) studied medicinal plants and is called father of botany

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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

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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

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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

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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

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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

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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.

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Botany / Evolution

Giving a name based on relationships. Possible through: -Evolution -taxonomy -DNA sequencing

Phylogenicity College 1/1 - 28 Genetic origin of

Synonyms Pinot Chardonnay, Beaunois, Morillon, Weißer Clevner and Feinburgunder Chardonnay- ( vinifera)

Phylogenetic origin of Chardonnay wine

Locus VVMD5

Locus VVMD28

Results: - : known by Romans - : 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) , (3) Auxerrois, (4) Bachet noir, (5) , (6) Chardonnay, (7) Franc noir de la Haute Saône, (8) blanc Gloriod, (9) Gamay noir, (10) Knipperlé, (11) Melon, (12) , (13) , (14) , (15) , (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 !

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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

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College 1/1 - 34 Ethnobotany - Ethnofarmacy

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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!

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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

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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

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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

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