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Natural products in pharmaceutical chemistry Nelson giovanny rincon silva

Overview about Natural Products in pharmaceutical chemistry

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Natural products in pharmaceutical chemistry Nelson giovanny rincon silva

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  2. 2. CONTENT Introduction – Natural Products Classes & Functions – Primary & Secondary Metabolites Basics Concepts Natural products: A continuing source of novel drug leads 2 Medicinal and Pharmaceutical Chemistry The Role of Traditional Medicine and Plants in Drug Discovery The Role of Marine Organisms in Drug Discovery Other Sources (Animals The Importance of Natural Products In Drug Discovery And Development Generals Ideas – Conclusions
  3. 3. 3 INTRODUCTION
  4. 4. 4 NATURAL PRODUCTS N.P´s are chemical compounds or substance produced by a living organism—that are found in nature. N.P´s sometimes have pharmacological or biological activity that can be of therapeutic benefit in treating diseases P. M. Dewick. Medicinal Natural Products, A Biosynthetic Approach. Second Edition (2002). John Wiley & Sons. England http://www.plantscience4u.com/2013/02/primary-and-secondary-metabolites.html#.VR99wvmG8o0
  5. 5. 5 CLASSES The broadest definition of N.P. is anything that is produced by life:  Biotic materials (e.g. wood, silk)  Bio-based materials (e.g. bioplastics, cornstarch)  Bodily fluids (e.g. milk, plant exudates)  Other natural materials (e.g. soil, coal). N.P´s may be classified according to their:  Biological function  Biosynthetic pathway  Source. P. M. Dewick. Medicinal Natural Products, A Biosynthetic Approach. Second Edition (2002). John Wiley & Sons. England
  6. 6. 6 NATURAL PRODUCTS Within the field of O.C., the N.P´s are usually restricted to mean purified organic compounds isolated from natural sources that are produced by the pathways:  Primary metabolism  Secondary metabolism P. M. Dewick. Medicinal Natural Products, A Biosynthetic Approach. Second Edition (2002). John Wiley & Sons. England Edit by: Giovanny Rincon-Silva O.C. : Organic Chemistry
  7. 7. 7 N.P´s are often divided into two major classes:  Primary metabolites: have an intrinsic function that is essential to the survival of the organism that produces them.  Secondary metabolites: have an extrinsic function that mainly affects other organisms. Some secondary metabolites have useful medicinal properties. Streptomycin, an important antibiotic drug produced by Streptomyces bacteria CLASSES & FUNCTIONS P. M. Dewick. Medicinal Natural Products, A Biosynthetic Approach. Second Edition (2002). John Wiley & Sons. England
  8. 8. 8 P.M. Components of basic metabolic pathways that are required for life. They are associated with essential cellular functions such as:  Nutrient assimilation  Energy production  Growth/development. Primary Metabolites Molecular building blocks of life P. M. Dewick. Medicinal Natural Products, A Biosynthetic Approach. Second Edition (2002). John Wiley & Sons. England Re wrote: Presenter
  9. 9. 9 S.M. Compounds that are not directly involved in the normal growth, development, or reproduction of an organism. Unlike P.M. absence of S.M. don’t result in immediate death, but rather the organism's survivability, fecundity or perhaps in no significant change at all. Humans use secondary metabolites as medicines, flavorings, and recreational drugs. Secondary metabolites P. M. Dewick. Medicinal Natural Products, A Biosynthetic Approach. Second Edition (2002). John Wiley & Sons. England http://myeclinik.com/tag/marijuana/
  10. 10. A. are produced by: Basic Concepts - Compounds P. M. Dewick. Medicinal Natural Products, A Biosynthetic Approach. Second Edition (2002). John Wiley & Sons. England http://thechive.com/2014/04/26/some-of-the-most-lethal-nopes-in-the-world-10-photos/venomous-poisonous-9/ Nicotiana tabacum Phyllobates terribilis 10
  11. 11. 11 A. possess psychotropic (e.g. psilocin) and stimulant activities (e.g. cocaine, caffeine, nicotine), and have been used in entheogenic rituals or as recreational drugs. The first individual alkaloid, morphine, was isolated in 1804 from the opium poppy (Papaver somniferum) P. M. Dewick. Medicinal Natural Products, A Biosynthetic Approach. Second Edition (2002). John Wiley & Sons. England Basic Concepts - Compounds
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  13. 13. 13 Terpenoids or isoprenoids, are a large and diverse class of naturally occurring organic chemicals similar to terpenes, derived from five-carbon isoprene units assembled and modified in thousands of ways Aflatoxin B1 is an aflatoxin produced by Aspergillus flavus and A. parasiticus. It is arguably the most potent carcinogen known and is up to twice as carcinogenic as an equitoxic dose of X-rays. P. M. Dewick. Medicinal Natural Products, A Biosynthetic Approach. Second Edition (2002). John Wiley & Sons. England Produced by certain living organisms in order to impart to them some survival advantage. Are biosynthesized by polymerization of acetyl propionyl Basic Concepts - Compounds
  14. 14. 14 Most of the S.M. of interest to humankind fit into categories which classify secondary metabolites based on their biosynthetic origin: Small "small molecules“ Codeine and Morphine, present in Papaver somniferum, the opium poppy Vincristine & Vinblastine, mitotic inhibitors found in the Rosy Periwinkle Secondary metabolites: Categories Cocaine Erythroxylon coca plant Solanaceae nightshade plant Scopolamine P. M. Dewick. Medicinal Natural Products, A Biosynthetic Approach. Second Edition (2002). John Wiley & Sons. England
  15. 15. 15 Azadirachtin, (Neem tree) tetrahydrocannabinol, present in cannabis Steroids (Terpenes) Saponins (plant steroids, often glycosylated) 5α-dihydroprogesterone (5α-DHP(−)-trans-Δ9- tetrahydrocannabinol Edit: Author P. M. Dewick. Medicinal Natural Products, A Biosynthetic Approach. Second Edition (2002). John Wiley & Sons. England Secondary metabolites: Categories
  16. 16. 16 Glycosides (heavily modified sugar molecules): Nojirimycin and Glucosinolates Phenazines: Phenazine-1-carboxylic acid (and derivatives) Biphenyls and dibenzofurans Beta-lactams: Penicillin, present in Penicillium fungi (See Later) Penicillin Natural phenols: Edit: Author P. M. Dewick. Medicinal Natural Products, A Biosynthetic Approach. Second Edition (2002). John Wiley & Sons. England Secondary metabolites: Categories
  17. 17. 17 Big "small molecules", produced by large, modular, "molecular factories“ Polyketides: Erythromycin (see before) Lovastatin and other statins Nystatin Rifamycin Fatty acid synthase products : FR-900848 phloroglucinols Lovastatin Nystatin P. M. Dewick. Medicinal Natural Products, A Biosynthetic Approach. Second Edition (2002). John Wiley & Sons. England Secondary metabolites: Categories
  18. 18. 18 Nonribosomal peptides: Ramoplanin Teicoplanin Gramicidin Bacitracin Ciclosporin Hybrids of the above three: Epothilone Polyphenols Non-"small molecules" – DNA, RNA, ribosome, or polysaccharide "classical" biopolymers Ribosomal peptides: Vancomycin Theaflavin-3-gallate, a plant derived polyphenol P. M. Dewick. Medicinal Natural Products, A Biosynthetic Approach. Second Edition (2002). John Wiley & Sons. England Staphylococcus aureus Secondary metabolites: Categories
  19. 19. 19 Plants, in particular, have formed the basis of sophisticated traditional medicine systems: 2600 BCE documenting the uses of approximately 1 000 plant-derived substances. Natural products: Historic Context A continuing source of novel drug leads http://laantiguamesopotamia.blogspot.com/ Commiphora species Treatment of ailments ranging from coughs and colds to parasitic infections and inflammation Edit: Author J.K. Borchardt, The beginnings of drug therapy: Ancient mesopotamian medicine, Drug News Perspect. 15 (2002) 187–192.
  20. 20. 20 Egyptian medicine dates from about 2900 BCE, but the best known record is the "Ebers Papyrus“. Dating from 1500 BCE, documenting over 700 drugs, mostly of plant origin The Chinese Materia Medica has been extensively documented over the centuries First about 1100 BCE (containing 52 prescriptions), followed by the Shennong Herbal 400 Drugs K.C. Huang, The pharmacology of chinese herbs, 2nd ed. CRC Press, Boca Raton, FL, 1999. Natural products: Historic Context A continuing source of novel drug leads
  21. 21. 21 Documentation of the Indian Ayurvedic system dates from before 1000 BCE (Charaka &Sushruta; Samhitas with 341 and 516 drugs respectively). Dhanvantari (धन्वंतरी), known as an avatar of Vishnu is the Hindu god associated with Ayurveda. S. Dev, Ancient-modern concordance in ayurvedic plants: Some examples, Environ. Health Perspect. 107 (1999) 783–789. Natural products: Historic Context A continuing source of novel drug leads
  22. 22. 22 Ayurveda: 8 ways to diagnose illness, called Nadi (pulse), Mootra (urine), Mala (stool), Jihva (tongue), Shabda (speech), Sparsha (touch), Druk (vision), and Aakruti (appearance) S. Dev, Ancient-modern concordance in ayurvedic plants: Some examples, Environ. Health Perspect. 107 (1999) 783–789. Natural products: Historic Context A continuing source of novel drug leads
  23. 23. 23 The Greeks and Romans contributed substantially to the rational development of the use of herbal drugs in the ancient Western world. Pedanius Dioscorides (Ancient Greek: Πεδάνιος Διοσκουρίδης; c. 40 – 90 AD)  Physician  pharmacologist  botanist D.S. Fabricant, N.R. Farnsworth, The value of plants used in traditional medicine for drug discovery, Environ. Health Perspect. 109 (2001) 69–75, (supplement). Author of De Materia Medica a encyclopedia about herbal medicine and related medicinal substances (A pharmacopeia) Was widely read for more than 1,500 years. Natural products: Historic Context A continuing source of novel drug leads
  24. 24. 24 Aelius Galenus or Claudius G.(Greek: Κλαύδιος AD 129 – c. 200/) known as Galen of Pergamon. Was a prominent Greek physician, surgeon and philosopher in the Roman empire. Arguably the most accomplished of all medical researchers of antiquity. D.S. Fabricant, N.R. Farnsworth, The value of plants used in traditional medicine for drug discovery, Environ. Health Perspect. 109 (2001) 69–75, (supplement). Natural products: Historic Context A continuing source of novel drug leads
  25. 25. 25 The Arabs preserved much of the Greco-Roman expertise during the Dark and Middle Ages (5th to 12th centuries) Abulcasis - Abu Al Qasim (936 - 1013), an surgeon at-Andalus, intellectual center of the Caliphate of Cordova wrote "Al - Tasrif" or Vade - Mecum, 30 volumes - presents all the knowledge of anatomy, physiology, nosology and therapy. Edit: Author D.S. Fabricant, N.R. Farnsworth, The value of plants used in traditional medicine for drug discovery, Environ. Health Perspect. 109 (2001) 69–75, (supplement). Natural products: Historic Context A continuing source of novel drug leads
  26. 26. 26 In 1909 the American Chemical Society founded its ‘Division of Pharmaceutical Chemistry’; the division was later renamed as‘Division of Chemistry of Medicinal Products.’ In 1948 the term medicinal chemistry emerged, ‘Division of Medicinal Chemistry: Name of the field: Medicinal chemistry Chimie thérapeutique Wikstofforschung Chimia Farmaceutica Farmacochemie 1973 a definition: ‘Medicinal chemistry concerns the discovery, the development, the identification and the interpretation of the mode of action of biologically active compounds at the molecular level. Emphasis is put on the discovery and development of drug, as indicated by the adjective ‘medicinal.’ Medicinal and Pharmaceutical Chemistry H. Timmerman, Medicinal and Pharmaceutical Chemistry, molecular Science and Chem, Engin. 123 (2013) 1-8
  27. 27. 27 Medicinal and Pharmaceutical Chemistry Edit: Author H. Timmerman, Medicinal and Pharmaceutical Chemistry, molecular Science and Chem, Engin. 123 (2013) 1-8 The urgent need for new pharmaceuticals for the treatment of cancer, HIV and other infectious diseases, demands a exploration to drug discovery and it is clear that Nature has played, and will continue to play a vital role in this process.
  28. 28. 28 Plant-based systems continue to play an essential role in healthcare WHO estimated in 1985 that approximately 65% of the population of the world predominately relied on plant-derived traditional medicines for their primary health care The Role of Traditional Medicine and Plants in Drug Discovery Ammi Visnaga Bronchodilator Galega OfficinalisAntidiabetic drug M. Gordon, C. David, Newman. Natural products: A continuing source of novel drug leads, Biochimica et Biophysica Acta 1830 (2013) 3670-3695.
  29. 29. 29 The Role of Traditional Medicine and Plants in Drug Discovery Papaver somniferum Used in the treatment of hypertension M. Gordon, C. David, Newman. Natural products: A continuing source of novel drug leads, Biochimica et Biophysica Acta 1830 (2013) 3670-3695.
  30. 30. 30 The Role of Traditional Medicine and Plants in Drug Discovery Natural antimalarial agents and analogues: Cinchona species M. Gordon, C. David, Newman. Natural products: A continuing source of novel drug leads, Biochimica et Biophysica Acta 1830 (2013) 3670-3695. Anopheles
  31. 31. 31 Plants have a long history of use in the treatment of cancer, though many of the claims for the efficacy of such treatment should be viewed with some skepticism The Role of Traditional Medicine and Plants in Drug Discovery M. Gordon, C. David, Newman. Natural products: A continuing source of novel drug leads, Biochimica et Biophysica Acta 1830 (2013) 3670-3695. Catharanthus roseus Treatment of leukemia and Hodgkin's lymphoma.
  32. 32. 32 The Role of Traditional Medicine and Plants in Drug Discovery Paclitaxel (Taxol®), the most exciting plant-derived anticancer drug discovered in recent years, along with several key precursors (the baccatins) in the leaves of various Taxus species M. Gordon, C. David, Newman. Natural products: A continuing source of novel drug leads, Biochimica et Biophysica Acta 1830 (2013) 3670-3695 http://home.ccr.cancer.gov/connections/2008/Vol2_No1/features3.asp http://home.ccr.cancer.gov/connections/2008/Vol2_No1/features3.asp
  33. 33. 33 The world‘s oceans, covering more than 70% of the earth's surface, represent an enormous resource for the discovery of potential chemotherapeutic agents. The systematic investigation of marine environments as sources of N.B.A.A. began mid-1970s. 70’s -90´s: 3 000 new metabolites were reported from a variety of marine organisms 1003 new compounds covering just publications in 2010. These studies have clearly demonstrated that the marine environment is a rich source of bioactive compounds, many not found in terrestrial sources. The Role of Marine Organisms in Drug Discovery N.B.A.G. Novel Biologically active agents M. Gordon, C. David, Newman. Natural products: A continuing source of novel drug leads, Biochimica et Biophysica Acta 1830 (2013) 3670-3695.
  34. 34. 34 The complex alkaloid ecteinascidin 743 isolated from the colonial tunicate Ecteinascidia turbinata. It has been designed in Europe and the USA under the name Yondelis® (approved 2007) by the EMEA for the treatment of soft tissue sarcomas (STS). The Role of Marine Organisms in Drug Discovery M. Gordon, C. David, Newman. Natural products: A continuing source of novel drug leads, Biochimica et Biophysica Acta 1830 (2013) 3670-3695.
  35. 35. 35 Marine-derived anticancer agents are Halichondrin B, a complex polyether isolated of several sponge sources. Bryostatin 1 another complex macrolide originally isolated from the bryozoan, Bugula neritina The Role of Marine Organisms in Drug Discovery Bryozoan, Bugula neritina Sponge M. Gordon, C. David, Newman. Natural products: A continuing source of novel drug leads, Biochimica et Biophysica Acta 1830 (2013) 3670-3695.
  36. 36. 36 The serendipitous discovery of penicillin from the filamentous fungus, Penicillium notatum. In 1929 - broad therapeutic use of this agent in the 1940s. Ushered in a new era in medicine, "the Golden Age of Antibiotics", and promoted the intensive investigation of Nature as a source of novel bioactive agents The Role of Microorganisms in Drug Discovery. Alexander Fleming M. Gordon, C. David, Newman. Natural products: A continuing source of novel drug leads, Biochimica et Biophysica Acta 1830 (2013) 3670-3695.
  37. 37. 37 Microorganisms are a prolific source of structurally diverse bioactive metabolites and have yielded some of the most important products of the pharmaceutical industry. Antibacterial agents, such as the penicillins, Cephalosporins (Cephalosporium acremonium) Aminoglycosides, tetracyclines and other polyketides. The Role of Microorganisms in Drug Discovery. Cephalosporins Aminoglycosides Cephalosporium acremonium M. Gordon, C. David, Newman. Natural products: A continuing source of novel drug leads, Biochimica et Biophysica Acta 1830 (2013) 3670-3695.
  38. 38. 38 Immunosuppressive agents, such as the cyclosporins (from Trichoderma and Tolypocladium species) and rapamycin (from Streptomyces species) The Role of Microorganisms in Drug Discovery. Trichoderma and Tolypocladium species Streptomyces species M. Gordon, C. David, Newman. Natural products: A continuing source of novel drug leads, Biochimica et Biophysica Acta 1830 (2013) 3670-3695.
  39. 39. 39 The Role of Microorganisms in Drug Discovery. Cholesterol lowering agents, such as mevastatin (compactin; from Penicillium species) and lovastatin (from Aspergillus species) And anthelmintics and antiparasitic drugs, such as the ivermectins (from Streptomyces species) Aspergillus species Streptomyces species M. Gordon, C. David, Newman. Natural products: A continuing source of novel drug leads, Biochimica et Biophysica Acta 1830 (2013) 3670-3695.
  40. 40. 40 Antitumor Antibiotics: Are amongst the most important of the cancer chemotherapeutic agents, which include members of the anthracycline, the enediynes, and the staurosporines: The Role of Microorganisms in Drug Discovery. Mitomycin M. Gordon, C. David, Newman. Natural products: A continuing source of novel drug leads, Biochimica et Biophysica Acta 1830 (2013) 3670-3695.
  41. 41. 41 The Role of Microorganisms in Drug Discovery. The epothilones isolated from myxobacteria have emerged as some of the most interesting natural product base structures being considered as agents for clinical trials in chemotherapy. These macrolides, with a mechanism of action similar to that of paclitaxel (Taxol®) http://www.for1406.uni-muenchen.de/index.html M. Gordon, C. David, Newman. Natural products: A continuing source of novel drug leads, Biochimica et Biophysica Acta 1830 (2013) 3670-3695.
  42. 42. 42 A notable discovery was the isolation of exendin-4 from the venom of the Gila monster, Heloderma suspectum led to the development of the extenatide polypeptide, Byetta®. . Other Sources (Animals) http://reptilefacts.tumblr.com/post/38234059618/u M. Gordon, C. David, Newman. Natural products: A continuing source of novel drug leads, Biochimica et Biophysica Acta 1830 (2013) 3670-3695. An injectable medicine used to improve glucose (blood sugar) control in type 2 diabetes
  43. 43. 43 Epibatidine, isolated from the skin of the poisonous frog, Epipedobates tricolor, has led to the development of a novel class of potential painkillers Other Sources (Animals) http://www.dendrobase.de/html/D_epipedobates_anthonyi.html The natural habitat is the Andean slopes of the central Ecuadorian Bolívar Province and Cotopaxi Province, (Ecuador). M. Gordon, C. David, Newman. Natural products: A continuing source of novel drug leads, Biochimica et Biophysica Acta 1830 (2013) 3670-3695.
  44. 44. 44 Predatory gastropods that belong to the genus Conus are marine animals, with 700 species. Cone snails have developed a deadly envenomation strategy that is used in prey capture and in defense and is perceived to play an important role in its evolutionary success. Vermivorous (worm hunters) Molluscivorous (mollusc hunters) Piscivorous (fish hunters) Other Sources (Animals) http://darkerview.com/wordpress/?tag=snail J. Prashanth, J. Richard, Lewis. Towarrds an integrated venomics approach for accelerated conopeptide discovery, Toxicon 60 (2012) 470-477.
  45. 45. 45 Other Sources (Animals) Venom comprising numerous small, cysteine rich peptides called conotoxins or conopeptides Along with analogues of endogenous signalling peptides and linear peptides. Most conopeptides range between 10 and 30 amino acids in length and each cone snail species produces venom comprising over 1000 unique peptides. It is currently estimated that there are 50 000 different conopeptides of which less than 0.1 % have been characterized to date Mu-conotoxin J. Prashanth, J. Richard, Lewis. Towarrds an integrated venomics approach for accelerated conopeptide discovery, Toxicon 60 (2012) 470-477.
  46. 46. 46 Other Sources (Animals) J. Prashanth, J. Richard, Lewis. Towarrds an integrated venomics approach for accelerated conopeptide discovery, Toxicon 60 (2012) 470-477.
  47. 47. 47 Other Sources (Animals) The high selectivity by showing conotoxins receptors and ion channels could allow use as drugs to treat various neuropathies. The most notable example to date is the Ziconotide drug. This compound is the synthetic form of the w- conotoxin MVIIA, Conus magus which blocks N-type calcium channel. The Ziconotide was evaluated as a drug to block chronic pain in patients with terminal cancer and AIDS, and its power and effectiveness are higher than related drugs Is a thousand times more potent than morphine and is not addictive. https://venomstodrugs.wordpress.com/current-venom-drugs/ J. Prashanth, J. Richard, Lewis. Towarrds an integrated venomics approach for accelerated conopeptide discovery, Toxicon 60 (2012) 470-477.
  48. 48. 48 Teprotide: isolated from the venom of the pit viper, Bothrops jararaca, led to the design and synthesis of the ACE inhibitors: treatment of hypertension. Captopril and enalapril used in the treatment of cardiovascular disease Other Sources (Animals) M. Gordon, C. David, Newman. Natural products: A continuing source of novel drug leads, Biochimica et Biophysica Acta 1830 (2013) 3670-3695. ACE: angiotensin-converting-enzyme inhibitor
  49. 49. 49 Other Sources (Animals) Dendroaspis polylepis (black mamba) is probably the most feared snake in Africa, making it a popular icon in movies and even a “street name” for certain psychoactive illegal drugs. (family Elapidae): Category 1 by WHO in 17 countries in sub-Saharan Africa: to species of ‘highest medical importance’, i.e. as ‘highly venomous snakes. http://3oneseven.com/green-mamba/http://wallpapers111.com/black-mamba-hd-wallpapers/ H. Andreas, B. Lomonte, B.Lohse, J. Fernández, J.M.Gutiérrez. Unveiling the nature of black mamba (Dendroaspis polylepis) venom through venomics and antivenom immunoprofiling: Identification of key toxin targets for antivenom development, Journal Of Proteomics 119 (2015) 126 – 142
  50. 50. 50 Other Sources (Animals) Effects: Paresthesia, strange taste in the mouth, nausea, retching, vomiting, abdominal pain, diarrhea, sweating, salivation, “gooseflesh”, and conjunctival congestion. Neurotoxicity: eliciting effects such as Ptosis Diplopia Dysphagia Flaccid paralysis Slurred speech Dyspnea due to respiratory muscle paralysis Involuntary skeletal muscle contractions. Associated with Hemorrhage, or necrosis. H. Andreas, B. Lomonte, B.Lohse, J. Fernández, J.M.Gutiérrez. Unveiling the nature of black mamba (Dendroaspis polylepis) venom through venomics and antivenom immunoprofiling: Identification of key toxin targets for antivenom development, Journal Of Proteomics 119 (2015) 126 – 142
  51. 51. 51 Other Sources (Animals) Dendrotoxins are unique components of the genus Dendroaspis Include metalloproteinase (MP), hyaluronidase (HYA), prokineticin (KTC), nerve growth factor (NGF), vascular endothelial growth factor (VEGF), phospholipase A2 (PLA2), 5′-nucleotidase (NUCL), and phosphodiesterase (PDE) families. Low amount of PLA2, which is an abundant component in the majority of elapid venom H. Andreas, B. Lomonte, B.Lohse, J. Fernández, J.M.Gutiérrez. Unveiling the nature of black mamba (Dendroaspis polylepis) venom through venomics and antivenom immunoprofiling: Identification of key toxin targets for antivenom development, Journal Of Proteomics 119 (2015) 126 – 142
  52. 52. 52 Other Sources (Animals) Mambalgins, which are members of the three-finger toxin family constitute 1.4% of the venom proteins. Model of mambalgins' structure. Similar to morphine, but without side effects II isoforms of mambalgin which have been given the names of M-1 and M-2. Both of these isopeptides : 57 aminoacidic chain with 8 residues of cysteine. Differ only in the residue located in the fourth position of the chain H. Andreas, B. Lomonte, B.Lohse, J. Fernández, J.M.Gutiérrez. Unveiling the nature of black mamba (Dendroaspis polylepis) venom through venomics and antivenom immunoprofiling: Identification of key toxin targets for antivenom development, Journal Of Proteomics 119 (2015) 126 – 142 Acid-Sensing Ion Channels (ASICs) are neuronal voltage-insensitive cationic channels activated by extracellular protons
  53. 53. 53 Scolopendra gigantea, also known as the Peruvian giant yellow-leg centipede or Amazonian giant centipede, is a representatives of the genus Scolopendra with a length up to 30 cm M. Gordon, C. David, Newman. Natural products: A continuing source of novel drug leads, Biochimica et Biophysica Acta 1830 (2013) 3670-3695. Other Sources (Animals) The Red Scorpion or Blue Scorpion (Rhopalurus junceus) is an endemic species, one of 36 different types of scorpion found on the islands of Cuba and Dominican Republic. http://www.havanatimes.org/sp/?p=16280
  54. 54. 54 The venom of the spider called the bananeras, one of the most powerful in the world It has medicinal properties for treating cardiac arrhythmia and cerebral ischemia. M. Gordon, C. David, Newman. Natural products: A continuing source of novel drug leads, Biochimica et Biophysica Acta 1830 (2013) 3670-3695. Other Sources (Animals) The PHKV toxin in the venom of this spider, inhibits atrial and ventricular arrhythmias Toxin using TX3-4 experiments showed neuroprotective action, reduced hippocampal cell death and restored the function of neurons affected by cerebral ischemia (stroke). Phoneutria nigriventer
  55. 55. 55 The Importance of Natural Products In Drug Discovery And Development analyzed the sources of new drugs over the period 1981-2014, and classified these compounds as: N (an unmodified natural product) NB (a natural product botanical) ND (a modified natural product) S (a synthetic compound with no natural product conception) S* , S*/NM (a synthetic compoundwith a natural product pharmacophore; /NM indicating competitive inhibition) S/NM (a synthetic compound showing competitive inhibition of the natural product substrate). M. Gordon, C. David, Newman. Natural products: A continuing source of novel drug leads, Biochimica et Biophysica Acta 1830 (2013) 3670-3695.
  56. 56. 56 1073 small molecule, new chemical entities (NCEs): 66% of the “formally synthetic”. 17%: molecules containing pharmacophores derived directly from N.P´s classified as S* and S*/NM. 14% are actually modeled on a N.P. inhibitor of the molecular target of interest (i.e. competitively inhibit) the endogenous substrate of the active site (S/NM). Only 36% can be classified as truly synthetic (i.e., devoid of natural) in origin (S) The Importance of Natural Products In Drug Discovery And Development M. Gordon, C. David, Newman. Natural products: A continuing source of novel drug leads, Biochimica et Biophysica Acta 1830 (2013) 3670-3695.
  57. 57. 57 GENERALS IDEAS – CONCLUSIONS All humanity benefits from the discovery of new drugs, all societies should collaborate in the preservation and evaluation of the areas of great diversity from which such structures might emerge. This could be carried out through investments made by pharmaceutical companies to help preserve this type of land. From the beginning of time N.P´s have been used as medicines for humanity, this use has become more sophisticated with the passage of time, until the development of sciences for study such as biology and chemistry. In fact, this has contributed to develop new subareas of knowledge such as biochemistry and pharmacist.
  58. 58. 58 GENERALS IDEAS – CONCLUSIONS In the future, with the advent of genetic techniques that permit the isolation and expression of biosynthetic cassettes, microbes and their marine invertebrate hosts may well be the new frontier for natural products lead discovery, though plant endophytes also offer an exciting new resource.

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