RECERCA EN PRODUCTES NATURALS Amaryllidaceae com a recerca... · RECERCA EN PRODUCTES NATURALS Dr.…

Download RECERCA EN PRODUCTES NATURALS Amaryllidaceae com a recerca... · RECERCA EN PRODUCTES NATURALS Dr.…

Post on 25-Jan-2019

212 views

Category:

Documents

0 download

Embed Size (px)

TRANSCRIPT

<p>RECERCA EN PRODUCTES NATURALS</p> <p>Dr. Laura Torras Claveria; Luciana Tallini, Dr. Francesc</p> <p>Viladomat, Dr. JaumeBastida</p> <p>Seminarisde Recercade la Facultatde Farmcia</p> <p>27 de setembrede 2016</p> <p>Plantes ornamentals de la famlia Amaryllidaceaecom a font de </p> <p>compostos bioactius</p> <p>Hymenocallis littoralis</p> <p>Phaedranasadubia</p> <p>Crinum x powellii</p> <p>Galanthus nivalis</p> <p>Lycoris radiata</p> <p>Narcissuscv. Pinza</p> <p>AMARYLLIDACEAE</p> <p>1981-2010</p> <p>Newman &amp; Cragg, J Nat Prod 2007, 70, 461-477</p> <p>Newman &amp; Cragg, J Nat Prod 2012, 75, 311-335</p> <p>Natural Products</p> <p>All newapproveddrugs</p> <p>Natural product and/or natural product structures play a highly significant role in the drug discovery and development </p> <p>New drugs Pre-clinic Clinic assays (Phases I-III)FDA Revision</p> <p>Production/ Phase IV</p> <p>5 Years 1,5 Years 6 Years 2 Years 2 Years</p> <p>Pre</p> <p>sen</p> <p>taci</p> <p>n</p> <p> ND</p> <p>A</p> <p>Pre</p> <p>sen</p> <p>taci</p> <p>n</p> <p> IN</p> <p>D</p> <p>5 compounds</p> <p>Average time in each step</p> <p>250 compunds</p> <p>IND: InvestigationalNew Drug</p> <p>NDA: New DrugApplication</p> <p>Research and development </p> <p>of new products</p> <p>1 approved drugFDA</p> <p>10.000compounds</p> <p>AmaryllidaceaefamilyBulbous plant family with ornamental and medical value</p> <p>3 subfamilies: Agapanthoideae, Allioideae, and Amaryllidoideae(previously 3 families)</p> <p>Term Amaryllidaceae</p> <p>corresponds with subfamily Amaryllidoideae</p> <p>Hippocrates of Kos (460-370 BC). Narcissus oil</p> <p>Uterus tumors</p> <p>Dioscorides(40-90 AD)Soranusof Ephesus (98-138 AD)</p> <p>Same therapy</p> <p>Pliny the Elder (23-79 AD)Topic use</p> <p>Narcissus extracts</p> <p>BibleNarcissus tazetta</p> <p>Anti-tumor therapy</p> <p>Middle AgesChinese medicine, N Africa</p> <p>Narcissus oil</p> <p>European doctorsHymenocalliscaribaeatumors inflammation</p> <p>Amaryllidaceaemedical uses through History</p> <p>Amaryllidaceaegeographical distribution</p> <p>Amaryllidaceae: Africa</p> <p>Amaryllidaceae: America</p> <p>Hymenocalliscoronaria(Alabama)</p> <p>Amaryllidaceae: Asia</p> <p>Amaryllidaceae: EuropeMediterranean area</p> <p>Caucasus</p> <p>Narcissus poeticus(Vall , Catalonia)</p> <p>Amaryllidaceaealkaloids</p> <p>6</p> <p>4a</p> <p>1</p> <p>4a</p> <p>10b10a</p> <p>10</p> <p>9</p> <p>8</p> <p>7 6</p> <p>12</p> <p>11</p> <p>4</p> <p>3</p> <p>2</p> <p>norbelladine lycorine homolycorine</p> <p>crinine narciclasinehaemanthamine</p> <p>tazettine</p> <p>montanine</p> <p>6a'</p> <p>43</p> <p>2</p> <p>16</p> <p>5</p> <p>1'2'</p> <p>3'</p> <p>4' 6'5'</p> <p>12 11</p> <p>3</p> <p>21</p> <p>4</p> <p>4a</p> <p>10b10a</p> <p>6a7</p> <p>109</p> <p>8</p> <p>12</p> <p>3</p> <p>4</p> <p>4a10b</p> <p>10a</p> <p>6a 6</p> <p>10</p> <p>9</p> <p>87</p> <p>1</p> <p>11</p> <p>12</p> <p>32</p> <p>66a</p> <p>10a10</p> <p>7</p> <p>8</p> <p>910b</p> <p>4</p> <p>7 6</p> <p>11</p> <p>4</p> <p>1</p> <p>2</p> <p>10b</p> <p>4a</p> <p>10a</p> <p>6a</p> <p>3</p> <p>8</p> <p>910</p> <p>1</p> <p>4</p> <p>4a12</p> <p>11</p> <p>6</p> <p>6a7</p> <p>10</p> <p>8</p> <p>911a 2</p> <p>3</p> <p>10a</p> <p>1210a</p> <p>6a7</p> <p>8</p> <p>910</p> <p>11 12</p> <p>1</p> <p>23</p> <p>4</p> <p>4a</p> <p>10b</p> <p>6</p> <p>galanthamine</p> <p>NH</p> <p>HO</p> <p>HO</p> <p>HO</p> <p>N</p> <p>O</p> <p>O</p> <p>OH</p> <p>HO</p> <p>H</p> <p>H</p> <p>O</p> <p>MeN</p> <p>MeO</p> <p>MeO</p> <p>H</p> <p>H</p> <p>O</p> <p>H</p> <p>NH</p> <p>OH</p> <p>O</p> <p>O</p> <p>O</p> <p>NMe</p> <p>OMe</p> <p>H</p> <p>OH</p> <p>O</p> <p>O</p> <p>4a</p> <p>1</p> <p>11</p> <p>12</p> <p>32</p> <p>66a</p> <p>10a10</p> <p>7</p> <p>8</p> <p>910b</p> <p>4</p> <p>NH</p> <p>OMe</p> <p>O</p> <p>O</p> <p>OH</p> <p>NH</p> <p>OH</p> <p>OH</p> <p>OH</p> <p>H</p> <p>OH O</p> <p>O</p> <p>O</p> <p>N</p> <p>OMe</p> <p>OHO</p> <p>O H</p> <p>O</p> <p>NMe</p> <p>MeO</p> <p>OH</p> <p>Other Amaryllidaceaealkaloids</p> <p>O</p> <p>NMeO</p> <p>O</p> <p>4a</p> <p>10b</p> <p>GracilineEsqueleto dibenzo[b,d]piranoConfiguracin absoluta 4aR/10bR</p> <p>RR</p> <p>Galanthus gracilisGalanthus plicatus ssp byzantinusPancratium maritimum</p> <p>N</p> <p>NMeO</p> <p>O</p> <p>OMe</p> <p>H</p> <p>O</p> <p>O</p> <p>OH</p> <p>H</p> <p>PlicamineCompuesto dinitrogenado no dimricoCentro spiro = Tazettina [O/N]</p> <p>Galanthus plicatus ssp byzantinusCyrthantus obliquus</p> <p>Graciline Plicamine</p> <p>Dibenzo[b,d] piranskeletonAbsolute configuration 4aR/10bR</p> <p>GalanthusgracilisGalanthusplicatusssp. ByzantinusPancratiummaritimum</p> <p>Non dimeric dinitrogenatedcompoundSpiro center = Tazettine[O/N]</p> <p>Galanthusplicatusssp. ByzantinusCyrthantusobliquusNarcissus broussonetii</p> <p>Exceptions</p> <p>NMe</p> <p>O</p> <p>O</p> <p>O</p> <p>O</p> <p>O</p> <p>H</p> <p>H O</p> <p>NMe</p> <p>O</p> <p>OH</p> <p>HO</p> <p>MeO</p> <p>NMe2</p> <p>ONMe2</p> <p>O NMe</p> <p>OMe</p> <p>O</p> <p>OMe</p> <p>NMe</p> <p>OMe</p> <p>OH</p> <p>OMe</p> <p>(-)-capnoidineFumariaceae</p> <p>(+)-bulbocapninePapaveraceae, Fumariaceae yLauraceae</p> <p>amisineAizoaceaeHymenocallis arenicolaZ Chem 1980, 20: 298</p> <p>mesembrenolAizoaceaeCrinum oliganthumZ Chem 1981, 21: 358</p> <p>mesembrenoneAizoaceaeNarcissus pallidulusJ Nat Prod 1989, 52: 478</p> <p>NH</p> <p>HO</p> <p>MeO</p> <p>salsolineChenopodiaceae (Salsola richteri)Galanthus woronowii</p> <p>Me</p> <p>Galanthus nivalis ssp cilicicusBiochem Syst Ecol 2004, 32, 1059</p> <p>Biochem Syst Ecol 2013, 51, 276</p> <p>Chemotaxonomic value</p> <p>O</p> <p>NMe</p> <p>O</p> <p>NMe</p> <p>COO</p> <p>NMe</p> <p>COOH</p> <p>Shihunine</p> <p>Dehidroshihunine</p> <p>H</p> <p>BehriatenuifloraGreene</p> <p>Amaryllidaceae AlliaceaeBastida, Sells, Codina, Viladomat, Len de la LuzPlanta Medica 1996, 62, 575-577</p> <p>Amaryllidaceaealkaloids biosynthesis</p> <p>trans-cinnamic acid, R1=R2=Hpara-coumaric acid, R1=OH, R2=Hcaffeic acid, R1=R2=OH</p> <p>tyramine</p> <p>Tyr-decarboxylase</p> <p>protocatechuic aldehyde</p> <p>PAL</p> <p>L-TyrL-Phe</p> <p>HO</p> <p>H2N COOH</p> <p>HO</p> <p>H2N</p> <p>COOH</p> <p>R1</p> <p>R2 CHO</p> <p>HO</p> <p>HO</p> <p>NH2</p> <p>COOH</p> <p>1.- Enzimaticpreparation of precursors</p> <p>-oxidation</p> <p>PAL</p> <p>hydroxylases</p> <p>reduction</p> <p>Tyr-decarboxylase</p> <p>CHO</p> <p>HO</p> <p>HO</p> <p>HO</p> <p>H2N</p> <p>N</p> <p>HO</p> <p>HONH</p> <p>HO</p> <p>O</p> <p>H</p> <p>N</p> <p>HOHOHO</p> <p>HO</p> <p>OH</p> <p>H</p> <p>NH</p> <p>HO</p> <p>HO</p> <p>HO</p> <p>tyramineprotocatechuic aldehyde</p> <p>Schiff's base(isomeric structures in solution)</p> <p>norbelladine</p> <p>Amaryllidaceaealkaloids biosynthesis2.- Primary ciclation</p> <p>Amaryllidaceaealkaloids biosynthesis</p> <p>3.- Enzimaticpreparation of intermediary agents</p> <p>MeO</p> <p>NHHO</p> <p>4'</p> <p>HO</p> <p>HO</p> <p>NHHO</p> <p>4'</p> <p>HO</p> <p>norbelladine O-methylnorbelladine</p> <p>Amaryllidaceaealkaloids biosynthesis</p> <p>4.- Secondary ciclation. Diversification</p> <p>types</p> <p>galanthamine</p> <p>types</p> <p>crinine haemanthaminetazettinenarciclasinemontanine</p> <p>types</p> <p>lycorinehomolycorine</p> <p>ortho-para' para-para' para-ortho'</p> <p>O-methylnorbelladine</p> <p>MeO</p> <p>NHHO</p> <p>4'</p> <p>HO</p> <p>Amaryllidaceaealkaloids biosynthesis</p> <p>4.- Secondary ciclation. Diversification</p> <p>types</p> <p>galanthamine</p> <p>types</p> <p>crinine haemanthaminetazettinenarciclasinemontanine</p> <p>types</p> <p>lycorinehomolycorine</p> <p>ortho-para' para-para' para-ortho'</p> <p>O-methylnorbelladine</p> <p>MeO</p> <p>NHHO</p> <p>OH</p> <p>Amaryllidaceaealkaloids biosynthesis</p> <p>4.- Secondary ciclation. Diversification</p> <p>types</p> <p>galanthamine</p> <p>types</p> <p>crinine haemanthaminetazettinenarciclasinemontanine</p> <p>types</p> <p>lycorinehomolycorine</p> <p>ortho-para' para-para' para-ortho'</p> <p>O-methylnorbelladine</p> <p>MeO</p> <p>NH</p> <p>OHOH</p> <p>Natural Products Research</p> <p>SCREENING STRUCTURAL CHARACTERIZATION</p> <p>Studyof genusNarcissus</p> <p>[Spain-Portugal]</p> <p>Studyof Amaryllidaceae</p> <p>spp. usedin TradMed[SA/Ibero-America]</p> <p>Studyof galanthamine</p> <p>producerspecies[Chemotaxonomy]</p> <p>Catalan flora</p> <p>19831980 20111993 2005I II III</p> <p>Phytochemical screening</p> <p>SCREENING</p> <p>Catalan flora</p> <p>19831980</p> <p>Collection, Drying, StorageTaxonomic DeterminationObtaining genus informationSimple method rapid selection</p> <p>NarcissusassoanusDuf.=N. requieniiRoem.</p> <p>=N. juncifoliusLag.</p> <p>(Amaryllidaceae)</p> <p>&gt; 1000 samples Green plants &amp; Fungus </p> <p>different habitats from Catalonia</p> <p>Natural Products Research</p> <p>SCREENING STRUCTURAL CHARACTERIZATION</p> <p>Studyof genusNarcissus</p> <p>[Spain-Portugal]</p> <p>Studyof Amaryllidaceae</p> <p>spp. usedin TradMed[SA/Ibero-America]</p> <p>Studyof galanthamine</p> <p>producerspecies[Chemotaxonomy]</p> <p>Catalan flora</p> <p>19831980 20111993 2005I II III</p> <p>Selection of genus Narcissus</p> <p>High content in exclusive AmaryllidaceaealkaloidsBiological and pharmacological activity of extracts and alkaloids previously isolated from this family speciesPoor studied genusInfluence area: Mediterranean (easy to work)</p> <p>In base of:</p> <p>Selection of genus Narcissus</p> <p>Distribution South Europe (Iberian Peninsula and Italy) (also in North Africa and East Mediterranean)</p> <p>80-100 speciesNarko(=narcotic) penetrating smell of flowers from some speciesGrowing from lowlands to highlandsFlowering at the end of winter - spring</p> <p>*</p> <p>*</p> <p>**</p> <p>Plant material</p> <p>Extracts FractionsPure </p> <p>compounds</p> <p>SpectroscopyUV, IR, MS, </p> <p>NMR (1D/2D), X Ray</p> <p>Structure elucidation</p> <p>Methodology</p> <p>Alkaloids from genus Narcissus</p> <p>N</p> <p>OH</p> <p>HO</p> <p>O</p> <p>OH</p> <p>H</p> <p>12</p> <p>3</p> <p>4</p> <p>4a</p> <p>6</p> <p>11</p> <p>12</p> <p>7</p> <p>10 10b</p> <p>6a8</p> <p>9 10a</p> <p>Lycorine, NarcissuspseudonarcissusGerrad, 1877: isolationNagakawaet al., 1956: characterization</p> <p>New alkaloids from Narcissus</p> <p>N</p> <p>HO</p> <p>MeO</p> <p>H</p> <p>H</p> <p>OR2</p> <p>R1O</p> <p>1-O-acetylpseudolycorine R1= Ac, R2= H2-O-acetylpseudolycorine R1= H, R2= Ac</p> <p>N</p> <p>MeO</p> <p>MeO</p> <p>oxoassoanine</p> <p>O</p> <p>O</p> <p>R1O</p> <p>R2O</p> <p>MeN</p> <p>H</p> <p>H</p> <p>O</p> <p>9</p> <p>9-O-demethylhomolycorine R1=H, R2= Me, R3= Hdubiusine R1= COCH2CHOHMe, R2= Me, R3= OAc9-O-demethyl-2 -hydroxyhomolycorine R1= H, R2= Me, R3= OH8-O-acetylhomolycorine R1= Me, R2= Ac, R3= H</p> <p>H</p> <p>NMe</p> <p>O</p> <p>O</p> <p>bicolorine</p> <p>R3</p> <p>N</p> <p>MeO</p> <p>MeO</p> <p>vasconine R= Htortuosine R= OMe</p> <p>N</p> <p>MeO</p> <p>MeO</p> <p>OMe</p> <p>roserine</p> <p>O</p> <p>R1O</p> <p>R2O</p> <p>MeN</p> <p>H</p> <p>H9</p> <p>H</p> <p>OMe</p> <p>O-methyllycorenine R1=R2= Me, R3=H2 -hydroxy-6-O-methyloduline R1+R2= CH2, R3=OH</p> <p>R3</p> <p>R</p> <p>New alkaloids from Narcissus</p> <p>OMeO</p> <p>OH</p> <p>N</p> <p>H</p> <p>O</p> <p>N-formylnorgalanthamine</p> <p>N</p> <p>OH</p> <p>HO</p> <p>MeO</p> <p>9</p> <p>H</p> <p>9-O-demethylmartidine</p> <p>OMeO</p> <p>NH</p> <p>epinorgalanthamine</p> <p>OMeO</p> <p>NH</p> <p>epinorlycoramine</p> <p>OH OH</p> <p>N</p> <p>OAc</p> <p>HO</p> <p>MeO</p> <p>9</p> <p>H</p> <p>cantabricine</p> <p>N</p> <p>OMe</p> <p>H</p> <p>11-O-acetylhaemanthamine</p> <p>N</p> <p>OMe</p> <p>H</p> <p>bujeine</p> <p>OAcO</p> <p>O</p> <p>O</p> <p>O</p> <p>MeCOOCH2</p> <p>O</p> <p>nangustine</p> <p>O</p> <p>O N H OH</p> <p>OH</p> <p>O</p> <p>NH</p> <p>HO H</p> <p>O</p> <p>O</p> <p>obesine</p> <p>O</p> <p>NMeO</p> <p>O</p> <p>OMe</p> <p>OOMe</p> <p>N</p> <p>HO</p> <p>pallidiflorine</p> <p>11</p> <p>Bastida, Lavilla, Viladomat. TheAlkaloids2006, 63, 87-179</p> <p>Natural Products Research</p> <p>SCREENING STRUCTURAL CHARACTERIZATION</p> <p>Studyof genusNarcissus</p> <p>[Spain-Portugal]</p> <p>Studyof Amaryllidaceae</p> <p>spp. usedin TradMed[SA/Ibero-America]</p> <p>Studyof galanthamine</p> <p>producerspecies[Chemotaxonomy]</p> <p>Catalan flora</p> <p>19831980 20111993 2005I II III</p> <p>Amaryllidaceaein traditional medicine</p> <p>KwaZulu-Natal200.000 Traditionalhealers(Year2004 licencesauthorization) South Africa</p> <p>Amaryllidaceaein traditional medicine</p> <p>Brunsvigia</p> <p>B. josephinaeB. orientalisB. radulosaB. littoralisB. bosmeniae</p> <p>CrinumC. sthulmaniiC. kirkiiC. delagoenseC. macowanii</p> <p>CyrtanthusC. elatusC.sanguineusC. obliquus</p> <p>Nerine</p> <p>N. filifolia</p> <p>stomach painLeprosy affected areas</p> <p>pregnancy (facilitate birth)</p> <p>sexually transmitted diseases (STD)lactation</p> <p>urinary problems</p> <p>South Africa</p> <p>Amaryllidaceaein traditional medicine</p> <p>AmmocharisA. tinneana</p> <p>BoophaneB. flava</p> <p>Used by indigenous population (Xhosa, Shoto, San, Zulu ...) Infusions of bulbs [&gt; 200 years]. A lot of species from genus Boophane, Brunsvigia, Crinum andNerineare used to treat infertility</p> <p>South Africa</p> <p>Plant material</p> <p>Extracts FractionsPure </p> <p>compounds</p> <p>Biological assays</p> <p>Mass spectrometryGC-MS, LC-MS</p> <p>SpectroscopyUV, IR, MS, </p> <p>NMR (1D/2D), X Ray</p> <p>Structure elucidation</p> <p>Methodology</p> <p>Amaryllidaceaealkaloids</p> <p>South Africa</p> <p>N</p> <p>OH</p> <p>H</p> <p>MeO</p> <p>HO</p> <p>N</p> <p>OAc</p> <p>OH</p> <p>R1</p> <p>R2</p> <p>H</p> <p>N</p> <p>O</p> <p>O</p> <p>OH</p> <p>OMe</p> <p>OMe</p> <p>HN</p> <p>O</p> <p>O</p> <p>OH</p> <p>OMe</p> <p>OMe</p> <p>H</p> <p>N</p> <p>OR2</p> <p>R1O</p> <p>R3</p> <p>O</p> <p>OH</p> <p>N</p> <p>O</p> <p>O</p> <p>OAc</p> <p>HO</p> <p>H</p> <p>N</p> <p>O</p> <p>O</p> <p>OMe</p> <p>AcO</p> <p>OMe</p> <p>HN</p> <p>O</p> <p>O</p> <p>OMe</p> <p>O</p> <p>OMe</p> <p>H</p> <p>N</p> <p>O</p> <p>O</p> <p>O NH</p> <p>OOR1</p> <p>OHOMe</p> <p>josephinine</p> <p>11-O-acetylambelline</p> <p>brunsbelline</p> <p>1-epibowdensine R1= R2= Ac, R3= OMe1-epidemethoxybowdensine R1= R2= Ac, R3= H1-epideacetylbowdensine R1= R2 =H, R3= OMe</p> <p>1</p> <p>delagoensine R1+R2= OCH2Odelagoenine R1= R2= OMe</p> <p>6 -hydroxycrinamidine R= H6 -hydroxyundulatine R= Me</p> <p>macowiine 6 -hydroxybuphanidrine</p> <p>filifoline</p> <p>OH</p> <p>Amaryllidaceaealkaloids</p> <p>South Africa</p> <p>N</p> <p>MeO</p> <p>HO</p> <p>H</p> <p>H</p> <p>HO</p> <p>NH</p> <p>H</p> <p>AcO</p> <p>O</p> <p>O</p> <p>OAc</p> <p>O</p> <p>O</p> <p>O</p> <p>HN</p> <p>O</p> <p>N</p> <p>NMeO</p> <p>O</p> <p>OMe</p> <p>O</p> <p>H</p> <p>H</p> <p>OH</p> <p>N</p> <p>O</p> <p>O</p> <p>OMe</p> <p>OH</p> <p>NMe</p> <p>MeO</p> <p>RO</p> <p>N</p> <p>MeO</p> <p>HO</p> <p>H</p> <p>H</p> <p>AcO</p> <p>NH</p> <p>MeO</p> <p>MeO</p> <p>MeO</p> <p>O</p> <p>O</p> <p>O</p> <p>N</p> <p>O</p> <p>kirkine</p> <p>buflavine R= Me8-O-demethylbuflavine R= H</p> <p>8</p> <p>montabuphine</p> <p>1-O-acetylnorpluviine</p> <p>obliquine</p> <p>1,2-O-diacetylzephyranthine</p> <p>noraugustamine 4a-dedihydronoraugustamine</p> <p>N-demethylbelladine</p> <p>Amaryllidaceaein Ibero-America</p> <p>Amaryllidaceaealkaloids</p> <p>Ibero-America</p> <p>N</p> <p>O</p> <p>O</p> <p>O N</p> <p>MeO</p> <p>MeO</p> <p>O</p> <p>H</p> <p>N</p> <p>MeO</p> <p>MeO</p> <p>OMe O</p> <p>NH</p> <p>O</p> <p>O</p> <p>O</p> <p>O</p> <p>NMeO</p> <p>O</p> <p>OMe</p> <p>OMe</p> <p>H</p> <p>H</p> <p>ungeremine oxomaritidine</p> <p>7-methoxyassoanine</p> <p>apohaemanthamine</p> <p>6-O-methylpretazettine</p> <p>MeO</p> <p>O</p> <p>NMe</p> <p>OH</p> <p>OH</p> <p>11 -hydroxygalanthamine</p> <p>Andrade, Berkov, Viladomat, Codina, Zuanazzi, BastidaMolecules2011,16, 7097-7104 (11 -hydroxygalanthamine)</p> <p>Amaryllidaceaemicropropagation</p> <p>Ibero-America</p> <p>Study of species in danger of extinctionStudy of insufficient samples</p> <p>Natural Products Research</p> <p>SCREENING STRUCTURAL CHARACTERIZATION</p> <p>Studyof genusNarcissus</p> <p>[Spain-Portugal]</p> <p>Studyof Amaryllidaceae</p> <p>spp. usedin TradMed[SA/Ibero-America]</p> <p>Studyof galanthamine</p> <p>producerspecies[Chemotaxonomy]</p> <p>Catalan flora</p> <p>19831980 20111993 2005I II III</p> <p>Galanthamine</p> <p>Galanthamine</p> <p>H3CO</p> <p>NCH3</p> <p>O</p> <p>OH Acetylcholinesteraseinhibitory activity</p> <p>Interaction with nicotinic receptors</p> <p>Commercialized for the treatment of mild to </p> <p>Geographic study Leucojumaestivum</p> <p>Distribution of different alkaloid types in Leucojumaestivumpopulations in Bulgaria</p> <p>Berkov, Georgieva, Kondakova, Viladomat, Bastida, Atanassov, CodinaBiochemical Systematics in Ecology 2013, 46, 152-161</p> <p>Methodology: GC-MS</p> <p>software AMDISAutomaticMassSpectralDeconvolutionand IdentificationSystem</p> <p>Separationand identificationof Amaryllidaceaealkaloids in complex mixtures and extracts without derivatisating</p> <p>Structural information of new compounds</p> <p>Differentiation of coelutingcompounds</p> <p>Methodology: GC-MS</p> <p>software AMDISAutomaticMassSpectralDeconvolutionand IdentificationSystem</p> <p>Identification of Amaryllidaceaealkaloids</p> <p>Amaryllidaceaealkaloids library NIST databaseLiterature</p> <p>KovatsRetention IndexMass spectra</p> <p>Methodology: GC-MSsoftware AMDIS</p> <p>GAL in ornamental Narcissus</p> <p>105 ornamental Narcissuscultivars were evaluated in terms of GAL content and AChEinhibitory activity, as a new source of GAL for pharmaceutical industry</p> <p>Torras-Claveria, Berkov, Codina, Viladomat, Bastida Industrial Cropsand Products, 2013, 43, 237-244 </p> <p>Narcissus hispanicus</p> <p>GAL in ornamental Narcissus</p> <p>GAL in ornamental Narcissus</p> <p>GAL in ornamental Narcissus</p> <p>Bulbs and leaves were evaluated separately</p> <p>Torras-Claveria, Berkov, Codina, Viladomat, Bastida Industrial Cropsand Products, 2013, 43, 237-244 </p> <p>GAL contentGC-MS</p> <p>AChEinhibitory activity</p> <p>In vitro test</p> <p>GAL content</p> <p>Torras-Claveria, Berkov, Codina, Viladomat, Bastida Industrial Cropsand Products, 2013, 43, 237-244 </p> <p>0</p> <p>1000</p> <p>2000</p> <p>3000</p> <p>4000</p> <p>5000</p> <p>6000</p> <p>7000</p> <p>8000</p> <p>N. confusus N. hispanicusYellow WingsRijnveld EarlySensation</p> <p>Rip VanWinkle</p> <p>g</p> <p> Ga</p> <p>l /g</p> <p> DW</p> <p>Galanthamine</p> <p>content in </p> <p>leaves</p> <p>0</p> <p>2000</p> <p>4000</p> <p>6000</p> <p>8000</p> <p>10000</p> <p>12000</p> <p>14000</p> <p>16000</p> <p>N. confususYellow WingsBella Estrella Enkele JonquillaSimplex</p> <p>N. hispanicus</p> <p>g</p> <p> Ga</p> <p>l/g D</p> <p>W</p> <p>Galanthamine</p> <p>content in </p> <p>bulbs</p> <p>AchEinhibitory activity</p> <p>Torras-Claveria, Berkov, Codina, Viladomat, Bastida Industrial Cropsand Products, 2013, 43, 237-244 </p> <p>0,000</p> <p>0,200</p> <p>0,400</p> <p>0,600</p> <p>0,800</p> <p>1,000</p> <p>1,200</p> <p>Snowball GreenHoward</p> <p>N. confusus Hawera Albus PlenusOdoratus</p> <p>PinkParadise</p> <p>N. hispanicus</p> <p>AC</p> <p>hEi</p> <p>nh</p> <p>ib. A</p> <p>ct.(</p> <p>IC50)</p> <p>0,000</p> <p>0,200</p> <p>0,400</p> <p>0,6