Reproduction de : Thèse Doctorat : Pharmacognosie : Metz : 1988. / 1988METZ023S.

Selected species of two South African rutaceous genera, Agathosma Willd. and Zanthoxylum L., were phytochemically studied. Two species of the former genus, A. puberula (Steud.) Fourc . and A. elavisepala R. A. Dyer, yielded a novel O-prenylcoumarin, puberul in, the structure of which was fully elucidated as 6,8- dimethoxy-7-prenyloxycoumarin. This represents the first report of a coumarin from that endemic genus. In another study the alkaloids in three species of Zanthoxylum, Z. davyi (Verdoorn) Waterm., Z. thorneroftii (Verdoorn) Waterm. and Z. humile (E .A. Bruce) Waterm . , were investigated. Chelerythrine, nitidine, (-) -α-N-methylcanadine, (+)-laurifoline and (+)-magnoflorine were isolated and characterized in the stem and root bark of Z. davyi, while the root bark of Z. thorneroftii contained skimmianine and decarine in addition to the alkaloids present in Z. davyi. Skimmianine, decarine, N-norchelerythrine, chelerythrine, (-)-α-N-methylcanadinc, candicine and tembetarine were identified in the root bark of Z. humile. The chemotaxonomic significance of these alkaloids occurring in the South African taxa in relation to other African Zanthoxylum taxa, is discussed. Several non-alkaloids (lupeol, β-sitosterol and (-)-sesamin) were also isolated and characterized in Z. davyi and Z. humile. Horizontal cellulose column chromatography and low pressure liquid chromatography have been applied to the separation of quaternary alkaloids

Chan Lai-Yin. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2003. / Includes bibliographical references (leaves 83-84). / Abstracts in English and Chinese. / Abstract --- p.i / Acknowledgements --- p.iii / Table of Contents --- p.iv / List of Abbreviations and symbols --- p.viii / List of Appendices --- p.x / List of Figures --- p.xi / List of Tables --- p.xii / Chapter Chapter 1: --- General Introduction --- p.1 / Chapter 1.1 --- Studies of Plant Constituents --- p.1 / Chapter 1.2 --- Extraction of Chemical Ingredients --- p.2 / Chapter 1.3 --- Separation and Purification of Chemical Ingredients --- p.2 / Chapter 1.3.1 --- Thin Layer Chromatography (TLC) --- p.3 / Chapter 1.3.2 --- Open Column Chromatography (OCC) --- p.4 / Chapter 1.4 --- Methods of Structural Identification --- p.4 / Chapter 1.4.1 --- Nuclear Magnetic Resonance (NMR) --- p.5 / Chapter 1.4.1.1 --- Proton NMR Spectroscopy (1H-NMR) --- p.5 / Chapter 1.4.1.2 --- Carbon-13 NMR Spectroscopy (13C NMR) --- p.5 / Chapter 1.4.1.3 --- Distortionless Enhancement by Polarization Transfer (DEPT) Experiment --- p.6 / Chapter 1.4.1.4 --- Two-dimensional Homonuclear Correlation Experiment --- p.6 / Chapter 1.4.1.5 --- Two-dimensional Heternuclear Chemical shift Correlation Experiment --- p.7 / Chapter 1.4.2 --- Mass Spectroscopy --- p.7 / Chapter 1.5 --- Literature Review --- p.8 / Chapter 1.5.1 --- Medical information on the genus Zanthoxylum --- p.8 / Chapter 1.5.2 --- Compounds found in the genus Zanthoxylum --- p.8 / Chapter 1.5.3 --- Compounds found in the Zanthoxylum acanthopodium --- p.9 / Chapter 1.5.4 --- Biological activities of the genus Zanthoxylum --- p.9 / Chapter 1.6 --- Research plan and Objectives of the present study --- p.16 / Chapter 1.7 --- References --- p.17 / Chapter Chapter 2: --- Materials and Methods --- p.20 / Chapter 2.1 --- General experimental procedures --- p.20 / Chapter 2.1.1 --- Solvents --- p.20 / Chapter 2.1.2 --- Chromatographic methods --- p.20 / Chapter 2.1.2.1 --- Normal phase chromatography --- p.20 / Chapter 2.1.2.2 --- Macro-reticular resinous adsorption chromatography --- p.20 / Chapter 2.1.3.3 --- Normal phase preparative thin layer chromatography --- p.21 / Chapter 2.1.3.4 --- Thin layer chromatography --- p.21 / Chapter 2.1.3 --- Determination of physical data --- p.21 / Chapter 2.1.3.1 --- Melting point determination --- p.21 / Chapter 2.1.3.2 --- Optical Rotation (OR) --- p.21 / Chapter 2.1.3.3 --- Ultraviolet (UV) absorption spectra --- p.22 / Chapter 2.1.3.4 --- Infra-red (IR) absorption spectra --- p.22 / Chapter 2.1.3.5 --- Nuclear Magnetic Resonance spectra (NMR) --- p.22 / Chapter 2.1.3.6 --- Mass Spectra (MS) --- p.22 / Chapter Chapter 3: --- Results / Chapter 3.1 --- "Procurement, extraction and initial fractionation of dried leaves and stem bark of Zahthoxylum acanthopodium" --- p.23 / Chapter 3.2 --- Chromatographic separation of the hexane and ethyl acetate extract --- p.24 / Chapter 3.2.1 --- Column chromatographic separation of fraction HEA-E --- p.24 / Chapter 3.2.1.1 --- Characterization of β -sitosterol --- p.24 / Chapter 3.2.2 --- Column chromatographic separation of fraction HEA-F --- p.25 / Chapter 3.2.2.1 --- Characterization of β -amyrin --- p.25 / Chapter 3.2.2.2 --- Characterization of 1 - octacosanol --- p.26 / Chapter 3.2.2.3 --- Characterization of (-)-sesamin --- p.26 / Chapter 3.2.3 --- Column chromatographic separation of fraction HEA-G --- p.27 / Chapter 3.2.3.1 --- Characterization of methyl hexacosanoate --- p.27 / Chapter 3.2.3.2 --- Characterization of methyl pluviatilol --- p.28 / Chapter 3.2.4 --- Column chromatographic separation of fraction HEA-H --- p.28 / Chapter 3.2.4.1 --- Characterization of (+)-methyl piperitol --- p.29 / Chapter 3.2.4.2 --- Characterization of (-)-epieudesmin --- p.29 / Chapter 3.2.5 --- Column chromatographic separation of fraction HEA-K --- p.29 / Chapter 3.2.5.1 --- Characterization of (+)-syringaresinol --- p.30 / Chapter 3.2.6 --- Column chromatographic separation of fraction HEA-M --- p.30 / Chapter 3.2.6.1 --- Characterization of daucosterol 6'-stearate --- p.31 / Chapter 3.2.7 --- Column chromatographic separation of fraction HEA-P --- p.31 / Chapter 3.2.7.1 --- Characterization of β -sitosterol- β -D-glucoside --- p.31 / Chapter 3.3 --- Chromatographic separation of the n-butanol extract --- p.32 / Chapter 3.3.1 --- Column chromatographic separation of fraction Bu-I --- p.32 / Chapter 3.3.1.1 --- Characterization of collettiside III --- p.32 / Chapter 3.3.1.2 --- Characterization of gracilline --- p.33 / Chapter Chapter 4: --- Discussion --- p.35 / Chapter 4.1 --- Isolated compounds --- p.35 / Chapter 4.1.1 --- Sterols --- p.35 / Chapter 4.1.1.1 --- Identification of -sitosterol --- p.36 / Chapter 4.1.1.2 --- Identification of β -sitosterol- β -D-glucoside --- p.41 / Chapter 4.1.1.3 --- Identification of daucosterol 6'-stearate --- p.45 / Chapter 4.1.2 --- Saponins --- p.50 / Chapter 4.1.2.1 --- Steroid glycosides --- p.51 / Chapter 4.1.2.1.1 --- Identification of collettiside III --- p.51 / Chapter 4.1.2.1.2 --- Identification of gracilline --- p.55 / Chapter 4.1.3 --- Terpenoid --- p.60 / Chapter 4.1.3.1 --- Identification of β -amyrin --- p.61 / Chapter 4.1.4 --- Lignans --- p.66 / Chapter 4.1.4.1 --- Identification of (-)-sesamin --- p.68 / Chapter 4.1.4.2 --- Identification of (-)-epieudesmin --- p.69 / Chapter 4.1.4.3 --- Identification of (+)-methyl piperitol --- p.70 / Chapter 4.1.4.4 --- Identification of methyl pluviatilol --- p.71 / Chapter 4.1.4.5 --- Identification of (+)-syringaresinol --- p.72 / Chapter 4.1.5 --- Alkanol --- p.78 / Chapter 4.1.5.1 --- Identification of 1 -octacosanol --- p.78 / Chapter 4.1.5.2 --- Identification of methyl hexacosanoate --- p.79 / Chapter 4.2 --- Conclusion --- p.81 / Chapter 4.3 --- References --- p.83

Thesis (M. Sc.)--University of Hong Kong, 1959. / Structures of new benzphenanthridine alkaloids from Zanthoxylum Nitidum, by H.R. Arthur, W.H. Hui and Y.L. Ng, in pocket in endpaper. Type-written copy. Includes bibliographical references (leaves 69-70).

No description available.

The present study was designed to evaluate the biological activity from the stem bark of Zanthoxylum rhoifolium and Zanthoxylum hyemale. The neutral methanol extract and fractions of this extract, the basic fractions that were obtained after acid-basic extraction from the methanolic extract, and pure compounds isolated from these fraction, were investigated in vitro for antimicrobial activity, antioxidant potential and for acetylcholinesterase inhibition. From the dichlorometane fraction of Zanthoxylum rhoifolium were isolated three furoquinoline alkaloids: skimianine, 8-hidroxy-4,7-dimetoxy-furoquinoline, and γ-fagarin, four benzophenantridine alkaloids: dihydrocheleritrine, dihydroavicine, zanthoxyline and cheleritrine. From the hexane fraction, the lignanes sesamine and lupeol were also isolated. From the neutral methanol extract were isolates de aporfinic alkaloid magnoflorine. The minimal inhibitory concentration of cheleritrine (MIC =1.50 μg/ml) for all tested bacteria, and between 3.12 and 12.5 μg/ml for the tested yeasts, showed this alkaloid have a excellent antimicrobial activity compared to chloramphenicol (between 3.5 to 6.25 μg/m for bacteria) and nistatin (between 5.5 to 10.3 μg/ml for yeasts). The study highlighted the antimicrobial activity of Z. rhoifolium stem bark. This activity is probably due their higher benzophenantridinic alkaloids level. The furoquinoline alkaloids, despite their insignificant antimicrobial activity, were the most active against the enzime AChE. In addition, in this work, the amide tembamide was isolated from the steam bark of Zanthoxylum hyemale, and their derivatives used for a structure-ativity analysis. / O presente estudo foi proposto para avaliar a atividade biológica da casca do caule de Zanthoxylum rhoifolium e Zanthoxylum hyemale. O extrato metanólico neutro e as frações deste extrato, as frações básicas obtidas após extração ácido-base do extrato metanólico e os compostos puros isolados dessas frações, foram avaliados in vitro quanto a atividade antimicrobiana, potencial antioxidante e inibição da enzima acetilcolinesterase. Da fração diclorometânica de Zanthoxylum rhoifolium foram isolados três alcalóides furoquinolínicos: skimianina, 8-hidroxi-4,7-dimetoxi-furoquinolinico e γ-fagarina, quatro alcalóides benzofenantridínicos: diidrocheleritrina, diidroavicina, zantoxilina e cheleritrina. Da fração hexânica foram isolados a lignana sesamina e o triterpeno lupeol. A partir do extrato metanólico neutro foi isolado o alcalóide aporfinico magnoflorina. A concentração inibitória mínima de cheleritrina (CIM = 1,50 μg/ml) para todas as bactérias testadas, e entre 3,12 e 12,5 μg/ml para as leveduras testadas, mostraram que este alcalóide possui uma excelente atividade antimicrobiana em comparação ao cloranfenicol (entre 3,5-6,25 μg/ml para as bactérias) e nistatina (entre 5,5-10,3 μg/ml para as leveduras). O estudo evidenciou a atividade antimicrobiana da casca do caule de Z. rhoifolium. Esta atividade é, provavelmente, devido ao seu alto nível de alcalóides benzofenantridínicos. Os alcalóides furoquinolinicos, mostraram pequena atividade antimicrobiana e foram os mais ativos frente a enzima AChE. Além disso, neste trabalho, a amida tembamida foi isolada da casca do caule de Zanthoxylum hyemale e seus derivados utilizados para uma análise de relação estrutura-atividade.

Please read the abstract in the section of 00front of this document / Thesis (PhD (Medical Plant Science))--University of Pretoria, 2008. / Plant Science / unrestricted

Four previously known dihydrobenzophenanthridine alkaloids, Dihydrochelerythrine (39), Bocconoline (42), Chelerythrine (2) and 6- Acetonyldihydrochelerythrine (33), were isolated from the stem bark of Zanthoxylum rhoifolium, along with other three lignans and the triterpen Lupeol (11). One of the lignans was identified as being sesamine (114), common in Zanthoxylum and the other two, already known, called Kaerophyllin (117) and Gadain (120) belong to dibenzylbutyrolactones. However, Kaerophyllin (117) and Gadain (120) were isolated for the first time from the Zanthoxylum rhoifolium. The structures of these metabolites were determined, mainly through spectroscopic methods, such as Nuclear Magnetic Resonance Spectroscopy 1H e 13 C (COSY, HMQC e HMBC), mass spectrometry and through the comparison of the data obtained from the melting point and data from the literature. The pure compounds and the hexane and eterea acid fractions, as well as chloroform basic fraction were tested for antitumor activity with nine cultured human tumor cell lines in vitro: MCF-7 (breast), NCI-ADR (breast with phenotype of the drug-resistant), UACC-62 (melanoma), NCI-460 (lung), PCO-3 (prostate), HT29 (colon), OVCAR (ovary), 786-0 (kidney) e K-562 (leukemia). The dihydrobenzophenanthridine alkaloids and the fractions showed more active, inhibiting the growth and provoking the death of several cell lines. On the other hand, the lignans showed no significant activity, being that, gadain (120) showed citostatic activity for all lines, only in the largest concentration tested. Through antimicrobial activity assays against Gram-positive bacteria: Staphylococcus aureus, Staphylococcus epidermidis and Bacillus subtilius; ramnegatives: Klebsiella pneumoniae, Pseudomonas aeruginosa, Escherichia coli and Salmonella setubal and fungi: Candida albicans, Candida dubliniensis, Sacharomyces cerevisiae and Cryptococcus neoformans, it was possible to observe that the alkaloids and the fractions were really active, mainly against bacteria. Chelerythrine (2) was the most active compound due to the growth inhibition of all the tested microorganisms, at the lowest concentration tested (0.15μg). The lignans were inactive against the tested microorganisms. The results found through the Microdilution Method showed that the alkaloid Chelerythrine presents a fungicide bacteriostatic property. / Quatro alcalóides benzofenantridínicos já conhecidos, Diidrocheleritrina (39), Bocconolina (42), Cheleritrina (2) e 6-Acetonildiidrocheleritrina (33), foram isolados da casca da raiz de Zanthoxylum rhoifolium, juntamente com outras três lignanas e o triterpeno Lupeol (11). Uma das lignanas foi identificada como sendo a Sesamina (114), comum no gênero Zanthoxylum e as outras duas pertencem à classe dibenzilbutirolactônica, denominadas de Kaerofilina (117) e Gadaina (120), ambas já conhecidas, porém foram isoladas pela primeira vez de Zanthoxylum rhoifolium. As estruturas destes metabólitos foram determinadas, principalmente, por métodos espectroscópicos, como a espectroscopia de Ressonância Magnética Nuclear 1H e 13 C (COSY, HMQC e HMBC), espectrometria de massas e através da comparação dos dados obtidos a partir do ponto de fusão e dados da literatura. Os compostos puros e as frações ácidas hexânica e etérea, bem como a fração clorofórmica básica foram submetidas a testes de atividade antitumoral com nove linhagens de culturas de células tumorais humanas in vitro: MCF-7 (mama), NCI-ADR (mama com fenótipo de resistência a múltiplas drogas), UACC-62 (melanoma), NCI-460 (pulmão), PCO-3 (próstata), HT-29 (cólon), OVCAR (ovário), 786-0 (rim) e K-562 (leucemia). Os alcalóides benzofenantridínicos e as frações apresentaram-se mais ativos, inibindo o crescimento e provocando a morte de diversas linhagens celulares. Já as lignanas apresentaram atividade pouco significativa, sendo que gadaina (120) exibiu atividade citostática para todas as linhagens, somente na maior concentração testada. Através dos ensaios de atividade antimicrobiana contra bactérias Grampositivas: Staphylococcus aureus, Staphylococcus epidermidis e Bacillus subtilius; Gram-negativas: Klebsiella pneumoniae, Pseudomonas aeruginosa, Escherichia coli e Salmonella setubal e fungos: Candida albicans, Candida dubliniensis, Sacharomyces cerevisiae e Cryptococcus neoformans, observou-se que os alcalóides e as frações foram bastante ativos, principalmente, contra bactérias. Cheleritrina (2) foi o composto mais ativo, devido à inibição de rescimento de todos os microrganismos testados, na menor das concentrações testadas (0,15μg). As lignanas não foram ativas contra os microrganismos testados. Através dos resultados obtidos pelo Método de Microdiluição, observou-se que o alcalóide cheleritrina apresenta caráter bacteriostático e fungicida.

Ces travaux de thèse concernent l’étude phytochimique de deux plantes médicinales appartenant aux genres Zanthoxylum (Rutaceae) et Bulnesia (Zygophyllaceae) connus pour leur utilisation en médecine traditionnelle, et plus particulièrement deux espèces endémiques des Andes Vénézuéliennes : Z. rhoifolium LAM et B. arborea Cl. Gay. L’étude des feuilles et des tiges de ces deux plantes a conduit à l’isolement de dix composés purs et complètement caractérisés : sept sont nouveaux (e.g., l’alcaloïde zanthoxyfoline, des saponines de types triterpène et ergostane) et l’un d’entre eux présente un squelette sesquiterpénique jusqu’alors jamais décrit (i.e., le bulnéarboréanoside I). / This work is a phytochemical study of two medicinal plants belonging to the genera Zanthoxylum (Rutaceae) and Bulnesia (Zygophyllaceae), which are known for their use in folk medecine, and in particular two endemic species of the Venezuelan Andes: Z. rhoifolium LAM and B. arborea Cl. Gay. The study of leaves and stems of these two plants led to the isolation of ten pure and fully characterized compounds: seven are new natural products (e.g., the alkaloid zanthoxyfoline, triterpene- and ergostane-types saponins) and one of them presents a sesquiterpene skeleton hitherto ever described (i.e., le bulnearboreanoside I).

Submitted by Ana Hilda Fonseca (anahilda@ufba.br) on 2016-09-01T17:22:47Z No. of bitstreams: 1 Tese Sandra Virginia A. Hohlemwerger.pdf: 5499646 bytes, checksum: 10ad62e0bf160a9a5e0326cba05adb7f (MD5) / Approved for entry into archive by Vanessa Reis (vanessa.jamile@ufba.br) on 2016-09-02T16:27:00Z (GMT) No. of bitstreams: 1 Tese Sandra Virginia A. Hohlemwerger.pdf: 5499646 bytes, checksum: 10ad62e0bf160a9a5e0326cba05adb7f (MD5) / Made available in DSpace on 2016-09-02T16:27:00Z (GMT). No. of bitstreams: 1 Tese Sandra Virginia A. Hohlemwerger.pdf: 5499646 bytes, checksum: 10ad62e0bf160a9a5e0326cba05adb7f (MD5) / Este trabalho tem como objetivo contribuir com o conhecimento fitoquímico das espécies do gênero Zanthoxylum. O presente estudo justifica-se devido ao escasso número de informações sobre a composição química de espécies deste gênero, endêmicas do Brasil, já que espécies pertencem a família Rutaceae vem sendo utilizadas na medicina popular em todo o mundo, inclusive no Brasil, e têm sido apontadas como potencial fonte para protótipos ou novos fármacos. A literatura correlaciona algumas atividades biológicas destas espécies com a presença de alcalóides, dentre eles os alcalóides benzilisoquinolínicos os quais além de serem relacionados com a atividade farmacológica são apontados como possíveis marcadores quimiossistemáticos. As espécies Zanthoxylum rhoifolium, Z. stelligerum e Z. tingoassuiba foram coletadas no semi-árido baiano e submetidas a procedimentos fitoquímicos convencionais os quais levaram a identificação dos alcalóides benzo[c]fenantridinicos (diidroqueleritina), (angolina), (arnotianamida) e (pseudo-norqueleritrina), do alcalóide protoberberínico (cis-N-metilcanadina iodeto) e do alcalóide pseudoprotoberberínico (2,3-metilenodioxi 10,11-dimetoxi tetrahidroprotoberberina iodeto) além disso também foi isolado o alcalóide aporfínico (predicentrina-metil-iodeto) e o alcalóide (metil antranilato de N-metila); as furanocumarinas (imperatorina) (xantotoxina) (isopipinelina) sendo ainda revelada a presença da lignana (senamina) e dos triterpenos (lupeol), (-amirina) e (amirinona), estes dois últimos encontrados apenas na cera epicuticular das folhas de Z. tingoassuiba. O óleo volátil das folhas de Z. tingoassuiba foi obtido pela extração com CO2 super crítico e através da hidrodestilação de onde foram identificados 06 monoterpenos, 10 sesquiterpenos e o alcalóide (metil antranilato de N-metila) este óleo apresentou atividade antifúngica, antibacteriana e capacidade de associação com lipossomas. As identificações destas substâncias foram efetuadas com base nos seus espectros de IV, RMN 1H e 13C uni e bidimensionais, cromatografia gasosa acoplada a espectrômetro de massas, espectrometria de massas por inserção direta e comparações com dados da literatura. Os metabólitos isolados e identificados nas espécies estudadas são condizentes com os já encontrados no gênero Zanthoxylum, como os alcalóides quaternários benzilisoquinolínicos e as furanocumarinas os quais estão associados ao caráter primitivo do gênero. Os resultados promissores das atividades biológicas, antifúngica, antibacteriana, antioxidante e antiparasitária, corroboram para a classificação deste gênero como fonte para o desenvolvimento de novos fármaco / This work aims to improve the knowledge phytochemical for the species of the genus Zanthoxylum. This study is justified due to the scarcity of information about the chemical composition of species of this genus, endemic to Brazil. Species belonging to family Rutaceae has been used in folk medicine around the world, including Brazil, have been identified as a potential source for prototypes or new drugs. The literature correlates the biological activities of some of these species with the presence of alkaloids, among them alkaloids benzylisoquinolines which besides being related to the pharmacological activity are considered possible chemical markers. Species Zanthoxylum rhoifolium, Z. stelligerum and Z. tingoassuiba were collected in semi- arid environments and subjected to conventional procedures phytochemicals which led to the identification of benzo [c] phenanthridine alkaloids (dihydrochelerythrine), (angoline), (arnottianamide) and (pseudo-norchelerythrine), and the protoberberínico alkaloid (cis-N-methylcanadine iodide) and pseudoprotoberberine alkaloid (2,3- methylendioxy 10,11-dimethoxy tetrahydroprotoberberine iodide) was also isolated the aporphine alkaloid (predicentrine-methiodide) and alkaloid (methyl N-methyl anthranilate); the furocumarins (imperatorin) (xanthotoxin) (isopimpinellin) besides the furofuran lignan (sesamin) and the triterpenoids (lupeol), (-amyrin) and (amyrinone) the latter two found only in the wax epicuticular on the leaves of Z. tingoassuiba. The volatile oil from leaves of Z. tingoassuiba was obtained by supercritical CO2 and by hydrodistillation of which were identified 06 monoterpenes, 10 sesquiterpenes and the alkaloid (methyl N-methyl anthranilate) this oil showed antifungal and antibacterial activity and ability to loaded into multilamellar liposomes. The identification of these substances was based on their IR spectra, 1H and 13C NMR single and two-dimensional, gas chromatography-mass spectrometry, mass spectrometry direct insertion, and comparison with literature data. The metabolites isolated and identified in the three species are consistent with those already found in the genus Zanthoxylum, such as quaternary benzylisoquinolines alkaloids and furnocumarinas which are associated with the primitive character of the genus. The promising results of biological activities, antifungal, antibacterial, antioxidant and anti- interference, collaborate with the classification of genus as a source for the development of new drugs.