The Iboga Alkaloids
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(12) United States Patent (10) Patent No.: US 8,859,764 B2 Mash Et Al
US008859764B2 (12) United States Patent (10) Patent No.: US 8,859,764 B2 Mash et al. (45) Date of Patent: Oct. 14, 2014 (54) METHODS AND COMPOSITIONS FOR 4,464,378 A 8, 1984 Hussain PREPARING NORIBOGAINE FROM 1999 A 5. E. E.ea. tal VOACANGINE 4,587,243 A 5/1986 LotSof 4,604,365. A 8, 1986 O'Neill et al. (75) Inventors: Deborah C. Mash, Miami, CA (US); 4,620,977 A 1 1/1986 Strahilevitz Robert M. Moriarty, Michiana Shores, 4,626,539 A 12/1986 Aungst et al. IN (US); Richard D. Gless, Jr., 2.s sy s: A : 3. E.OCS ca.t Oakland, CA (US) 4,737,586 A 4, 1988 Potier et al. 4,806,341 A 2f1989 Chien et al. (73) Assignee: DemeRx, Inc., Ft. Lauderdale, FL (US) 4,857,523 A 8, 1989 LotSof 5,026,697 A 6, 1991 LotSof (*) Notice: Subject to any disclaimer, the term of this 5,075,341. A 12, 1991 Mendelson et al. patent is extended or adjusted under 35 Sigi A 3. 3: E. al. U.S.C. 154(b) by 0 days. 5,152.994.J. I.- A 10/1992 Lotsofranger et al. 5,283,247 A 2f1994 Dwivedi et al. (21) Appl. No.: 13/496,185 5,290,784. A 3/1994 Quet al. 5,316,759 A 5/1994 Rose et al. (22) PCT Filed: Jan. 23, 2012 5,382,657 A 1/1995 Karasiewicz et al. 5,426,112 A 6/1995 Zagon et al. (86). PCT No.: PCT/US2012/022255 5,574,0525,552,406 A 1 9,1/1996 1996 MendelsonRose et al. -
Modifications on the Basic Skeletons of Vinblastine and Vincristine
Molecules 2012, 17, 5893-5914; doi:10.3390/molecules17055893 OPEN ACCESS molecules ISSN 1420-3049 www.mdpi.com/journal/molecules Review Modifications on the Basic Skeletons of Vinblastine and Vincristine Péter Keglevich, László Hazai, György Kalaus and Csaba Szántay * Department of Organic Chemistry and Technology, University of Technology and Economics, H-1111 Budapest, Szt. Gellért tér 4, Hungary * Author to whom correspondence should be addressed; E-Mail: [email protected]; Tel: +36-1-463-1195; Fax: +36-1-463-3297. Received: 30 March 2012; in revised form: 9 May 2012 / Accepted: 10 May 2012 / Published: 18 May 2012 Abstract: The synthetic investigation of biologically active natural compounds serves two main purposes: (i) the total synthesis of alkaloids and their analogues; (ii) modification of the structures for producing more selective, more effective, or less toxic derivatives. In the chemistry of dimeric Vinca alkaloids enormous efforts have been directed towards synthesizing new derivatives of the antitumor agents vinblastine and vincristine so as to obtain novel compounds with improved therapeutic properties. Keywords: antitumor therapy; vinblastine; vincristine; derivatives 1. Introduction Vinblastine (1) and vincristine (2) are dimeric alkaloids (Figure 1) isolated from the Madagaskar periwinkle plant (Catharantus roseus), exhibit significant cytotoxic activity and are used in the antitumor therapy as antineoplastic agents. In the course of cell proliferation they act as inhibitors during the metaphase of the cell cycle and by binding to the microtubules inhibit the development of the mitotic spindle. In tumor cells these agents inhibit the DNA repair and the RNA synthesis mechanisms, blocking the DNA-dependent RNA polymerase. Molecules 2012, 17 5894 Figure 1. -
Effect of Various Extracts of Tabernaemontana Divaricata on Haloperidol Induced Catalepsy in Rats
Raj et al., International Current Pharmaceutical Journal, February 2014, 3(3): 240-242 International Current http://www.icpjonline.com/documents/Vol3Issue3/02.pdf Pharmaceutical Journal ORIGINAL RESEARCH ARTICLE OPEN ACCESS Effect of various extracts of Tabernaemontana divaricata on haloperidol induced catalepsy in rats *Chanchal N. Raj1, A. Balasubramaniam2, Sayyed Nadeem2 1Department of Pharmacy, Karpagam University,Coimbatore, Tamilnadu, – 641021, India 2Technocrats Institute of Technology- Pharmacy, Bhopal, M.P.-462021, India ABSTRACT Parkinson’s disease (PD) is one of the neurodegenerative diseases with selective loss of dopamine neurons of the substantia n igra pars compacta. In the present study, anti-cataleptic activity of Tabernaemontana divaricata leaves extracts viz. aqueous and ethanolic at different doses (50, 100 and 150 mg/kg i.p.) were studied using haloperidol (1 mg/kg, i.p.) induced catalepsy in rats which is a useful animal model for screening drugs for Parkinson’s disease. Both the extracts were found to reduce catalepsy significantly (P<0.001) as compared to the haloperidol treated rats showing greater effect at 150 mg/kg i.p. dose. Thus the present study reveals the anti- cataleptic activity of Tabernaemontana divaricata evaluating the traditional folklore medicinal use of the plant. Key Words: Tabernaemontana divaricata, Parkinson’s disease (PD), catalepsy, haloperidol, bar test. INTRODUCTIONINTRODUCTION by the increase of the lipid peroxidation product, Neurological disorders include brain injuries, neuro- malonaldehyde. -
Studies on the Pharmacology of Conopharyngine, an Indole Alkaloid of the Voacanga Series
Br. J. Pharmac. Chemother. (1967), 30, 173-185. STUDIES ON THE PHARMACOLOGY OF CONOPHARYNGINE, AN INDOLE ALKALOID OF THE VOACANGA SERIES BY P. R. CARROLL AND G. A. STARMER From the Department of Pharmacology, University of Sydney, New South Wales, Australia (Received January 17, 1967) Conopharyngine, the major alkaloid present in the leaves of Tabernaemontana (Conopharyngia) pachysiphon var. cumminsi (Stapf) H. Huber was isolated and identified by Thomas & Starmer (1963). The same alkaloid has also been found in the stem bark of a Nigerian variety of the same species by Patel & Poisson (1966) and in the stem bark of Conopharyngia durissima by Renner, Prins & Stoll (1959). Conopharyn- gine is an indole alkaloid of the voacanga type, being 18-carbomethoxy-12,13- dimethoxyibogamine (Fig. 1) and is thus closely related to voacangine and coronaridine. Me.0OC Fig. 1. Conopharyngine (18-carbomethoxy-12,13-dimethoxyibogamine). Some confusion exists in that an alkaloid with an entirely different structure, but also named conopharyngine, was isolated from a cultivated variety of Conopharyngia pachysiphon by Dickel, Lucas & Macphillamy (1959). This compound was shown to be the 3-D-9-glucoside of 55-20a-amino-3 8-hydroxypregnene, and was reported to possess marked hypotensive properties. The presence of steroid alkaloids in the Tabernaemontaneae was hitherto unknown and it was suggested by Raffauf & Flagler (1960) and Bisset (1961) that the plant material was open to further botanical confir- mation. The roots of the conopharyngia species are used in West Africa to treat fever (Kennedy, 1936), including that of malaria (Watt & Breyer-Brandwijk, 1962). The only report on the pharmacology of conopharyngine is that of Zetler (1964), who included it in a study of some of the effects of 23 natural and semi-synthetic alkaloids 174 P. -
(12) United States Patent (10) Patent No.: US 8,940,728 B2
USOO894.0728B2 (12) UnitedO States Patent (10) Patent No.: US 8,940,728 B2 Mash et al. (45) Date of Patent: Jan. 27, 2015 (54) SUBSTITUTED NORIBOGAINE 5,152.994. A 10/1992 Lotsof 5,283,247 A 2f1994 Dwivedi et al. (71) Applicant: DemeRx, Inc., Miami, FL (US) 5,316,7595,290,784. A 3/19945/1994 Quetal.Rose et al. 5,382,657 A 1/1995 K. tal. (72) Inventors: Deborah C. Mash, Miami, FL (US); 5,426,112 A 6, 1995 ity a Richard D. Gless, Jr., Oakland, CA 5,552,406 A 9, 1996 Mendelson et al. (US); Robert M. Moriarty, Michiana 5,574,052 A 1 1/1996 Rose et al. Shores, IN (US) 5,578,645 A 11/1996 Askanazi et al. s 5,580,876 A 12/1996 Crain et al. 5,591,738 A 1, 1997 LotSof (73) Assignee: DemeRx, Inc., Miami, FL (US) 5,618,555 A 4/1997 Tokuda et al. - 5,703,101 A 12/1997 Rose et al. (*) Notice: Subject to any disclaimer, the term of this 5,726, 190 A 3, 1998 Rose et al. patent is extended or adjusted under 35 S.S.; A s 3. th. 1 U.S.C. 154(b)(b) bybV 144 davs.ayS 5,865.444.wwk A 2/1999 KempfetOSe et al. al. 5,925,634 A 7/1999 Olney (21) Appl. No.: 13/732,751 5,935,975 A 8/1999 Rose et al. 6,211,360 B1 4/2001 Glicket al. (22) Filed: Jan. 2, 2013 6,291.675 B1 9/2001 Coop et al. -
The Alkaloids: Chemistry and Biology
CONTRIBUTORS Numbers in parentheses indicate the pages on which the authors’ contributions begin. B. EMMANUEL AKINSHOLA (135), Department of Pharmacology, College of Medicine, Howard University, Washington, DC 20059, eakinshola@ howard.edu NORMA E. ALEXANDER (293), NDA International, 46 Oxford Place, Staten Island, NY 10301, [email protected] SYED F. ALI (79, 135), Division of Neurotoxicology, National Center for Toxicological Research, 3900 NCTR Road, Jefferson, AR 72079, [email protected] KENNETH R. ALPER (1, 249), Departments of Psychiatry and Neurology, New York University School of Medicine, 550 First Avenue, New York, NY 10016, [email protected] MICHAEL H. BAUMANN (79), Clinical Psychopharmacology Section, Intra- mural Research Program, NIDA, National Institutes of Health, Baltimore, MD 21224, [email protected] DANA BEAL (249), Cures-not-Wars, 9 Bleecker Street, New York, NY 10012, [email protected] ZBIGNIEW K. BINIENDA (193), Division of Neurotoxicology, National Cen- ter for Toxicological Research, 3900 NCTR Road, Jefferson, AR 72079, [email protected] WAYNE D. BOWEN (173), Laboratory of Medicinal Chemistry, NIDDK, NIH, Building 8 B1-23, 8 Center Drive, MSC 0820, Bethesda, MD 20892, [email protected] FRANK R. ERVIN (155), Department of Psychiatry and Human Genetics, McGill University, Montreal, Quebec H3A 2T5, Canada, md18@musica. mcgill.ca JAMES W. FERNANDEZ (235), Department of Anthropology, University of Chicago, 1126 E. 59th Street, Chicago, IL 60637, jwfi@midway. uchicago.edu xi xii CONTRIBUTORS RENATE L. FERNANDEZ (235), Department of Anthropology, University of Chicago, 1126 E. 59th Street, Chicago, IL 60637, rlf2@midway. uchicago.edu GEERTE FRENKEN (283), INTASH, P.O. -
Alkaloids with Anti-Onchocercal Activity from Voacanga Africana Stapf (Apocynaceae): Identification and Molecular Modeling
molecules Article Alkaloids with Anti-Onchocercal Activity from Voacanga africana Stapf (Apocynaceae): Identification and Molecular Modeling Smith B. Babiaka 1,2,*, Conrad V. Simoben 3 , Kennedy O. Abuga 4, James A. Mbah 1, Rajshekhar Karpoormath 5 , Dennis Ongarora 4 , Hannington Mugo 4, Elvis Monya 6, Fidelis Cho-Ngwa 6, Wolfgang Sippl 3 , Edric Joel Loveridge 7,* and Fidele Ntie-Kang 1,3,8,* 1 Department of Chemistry, Faculty of Science, University of Buea, P.O. Box 63, Buea CM-00237, Cameroon; [email protected] 2 AgroEco Health Platform, International Institute of Tropical Agriculture, Cotonou, Abomey-Calavi BEN-00229, Benin 3 Institute for Pharmacy, Martin-Luther-Universität Halle-Wittenberg, Kurt-Mothes-Str. 3, 06120 Halle, Germany; [email protected] (C.V.S.); [email protected] (W.S.) 4 Department of Pharmaceutical Chemistry, School of Pharmacy, University of Nairobi, Nairobi P.O. Box 19676–00202, Kenya; [email protected] (K.O.A.); [email protected] (D.O.); [email protected] (H.M.) 5 Department of Pharmaceutical Chemistry, School of Chemistry, University of KwaZulu-Natal, Durban 4001, South Africa; [email protected] 6 ANDI Centre of Excellence for Onchocerciasis Drug Research, Biotechnology Unit, Faculty of Science, University of Buea, P.O. Box 63, Buea CM-00237, Cameroon; [email protected] (E.M.); fi[email protected] (F.C.-N.) 7 Department of Chemistry, Swansea University, Singleton Park, Swansea SA2 8PP, UK 8 Institute of Botany, Technical University of Dresden, 01217 Dresden, Germany * Correspondence: [email protected] or [email protected] (S.B.B.); Citation: Babiaka, S.B.; Simoben, C.V.; [email protected] (E.J.L.); ntiekfi[email protected] or fi[email protected] (F.N.-K.) Abuga, K.O.; Mbah, J.A.; Karpoormath, R.; Ongarora, D.; Abstract: A new iboga-vobasine-type isomeric bisindole alkaloid named voacamine A (1), along with Mugo, H.; Monya, E.; Cho-Ngwa, F.; eight known compounds—voacangine (2), voacristine (3), coronaridine (4), tabernanthine (5), iboxy- Sippl, W.; et al. -
A Review on Tabernaemontana Spp.: Multipotential Medicinal Plant
Online - 2455-3891 Vol 11, Issue 5, 2018 Print - 0974-2441 Review Article A REVIEW ON TABERNAEMONTANA SPP.: MULTIPOTENTIAL MEDICINAL PLANT ANAN ATHIPORNCHAI* Department of Chemistry and Center of Excellence for Innovation in Chemistry, Faculty of Science, Burapha University, Bangsaen, Chonburi 20131 Thailand. Email: [email protected] Received: 01 March 2016, Revised and Accepted: 29 January 2018 ABSTRACT Plants in the genus Tabernaemontana have been using in Thai and Chinese traditional medicine for the treatment several diseases. The great majority constituents of Tabernaemontana species have already been subjected to isolation and identification of monoterpene indole alkaloids present in their several parts. Many of monoterpene indole alkaloids exhibited a wide array of several activities. The biogenesis, classification, and biological activities of these alkaloids which found in Tabernaemontana plants were discussed in this review and its brings the research up-to-date on the bioactive compounds produced by Tabernaemontana species, directly or indirectly related to human health. Keywords: Tabernaemontana plants, Phytochemistry, Biogenesis, Terpene indole alkaloids, Biological activities. © 2018 The Authors. Published by Innovare Academic Sciences Pvt Ltd. This is an open access article under the CC BY license (http://creativecommons. org/licenses/by/4. 0/) DOI: http://dx.doi.org/10.22159/ajpcr.2018.v11i5.11478 INTRODUCTION alkaloids are investigated. All monoterpene indole alkaloids are derived from aromatic amino acid tryptophan and the iridoid terpene Several already drugs were discovered from the natural products. secologanin (Scheme 1). Tryptophan converts to tryptamine using Especially, the treatments of infectious diseases and oncology have tryptophan decarboxylase which is a pyridoxal-dependent enzyme. benefited from numerous drugs which were found in natural product The specific iridoid precursor was subsequently identified as sources. -
UPS-QT11443.Pdf
UNIVERSIDAD POLITÉCNICA SALESIANA SEDE QUITO CARRERA: INGENIERÍA EN BIOTECNOLOGÍA DE LOS RECURSOS NATURALES Trabajo de titulación previo a la obtención del título de: INGENIERA EN BIOTECNOLOGÍA DE LOS RECURSOS NATURALES TEMA: INHIBICIÓN DE LA ACTIVIDAD HEMOLÍTICA DEL VENENO DE Bothrops atrox POR LOS EXTRACTOS DE Tabernaemontana sananho Ruiz & Pav. Y Mucuna cf. elliptica (Ruiz&Pav.) DC. AUTORA: JENNY VERÓNICA CUEVA PUNGACHO TUTOR: WILSON FABIÁN TAPIA HERNÁNDEZ Quito, marzo 2017 Dedicatoria Mi tesis la dedico con todo mi amor a Dios por haberme dado la vida y permitirme haber llegado hasta este momento tan importante de mi formación profesional. A mis padres Cecilia e Iván, a mis hermanos Lorena e Iván Cueva y mi Sobrinita Amelia por ser el pilar más importante en mi vida, demostrándome siempre su cariño, apoyo incondicional y sobre todo su confianza para culminar esta etapa de mi vida. A la compañera de toda la vida Birkha que fue quien en las noches frías de angustia siempre estuvo demostrándome su lealtad y cariño hasta su último suspiro. Agradecimiento Sin duda alguna mi profundo agradecimiento a la UNIVERSIDAD POLITÉCNICA SALESIANA que me dio la oportunidad de realizar mis sueños en la formación profesional con la ayuda de los maestros formadores de jóvenes con inspiraciones para un mañana lleno de sueños y formar un futuro de promesas para una vida mejor. Este proyecto es el resultado del esfuerzo conjunto de todos los que formamos el grupo de trabajo. De manera especial mi agradecimiento a mi tutor Químico Farmacéutico Wilson Tapia quien con su esfuerzo, dedicación y sobretodo con su profesionalismo que nos impartió sus conocimientos e hizo posible la culminación del proyecto. -
Gastroprotective Effect of Tabernaemontana Divaricata (Linn.) R.Br
British Journal of Pharmaceutical Research 1(3): 88-98, 2011 SCIENCEDOMAIN international www.sciencedomain.org Gastroprotective Effect of Tabernaemontana divaricata (Linn.) R.Br. Flower Methanolic Extract in Wistar Rats Mohammed Safwan Ali Khan1,2&3* 1Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, University Putra Malaysia, Serdang 43400, Selangor Darul Ehsan, Malaysia. 2Department of Pharmacognosy, Anwarul Uloom College of Pharmacy, New Mallepally, Hyderabad 500001, Andhra Pradesh, India. 3Department of Pharmaceutical Sciences, Nims University, Shobha Nagar, Delhi Highway, Jaipur - 303 121, Rajasthan, India. Received 24th April 2011 Accepted 2nd June 2011 Research Article Online Ready 6th June 2011 ABSTRACT Tabernaemontana divaricata (L.) R.Br belonging to Apocynaceae family is traditionally used by people in many parts of the world to treat various disorders. The present study was undertaken to investigate anti-ulcer property of Tabernaemontana divaricata flower methanolic extract (TDFME 500 mg/kg, p.o) by pyloric ligation induced gastric ulceration model using Omeprazole (8mg/kg, p.o) as a standard drug in wistar rats. Five parameters i.e., volume of gastric juice, pH, free & total acidities and ulcer index were assessed. The test extract significantly (p< 0.01) decreased volume of gastric juice, free & total acidities and ulcer index. Like standard, it also raised pH of gastric acid. The observed percentage protection for standard and test were 89.84% and 79.53%, respectively. Thus, TDFME 500 mg/kg had a positive effect on all the parameters under study and the results were similar to that of standard. From the above results, it can be concluded that TDFME exhibits remarkable gastroprotective effect. -
Near the Himalayas, from Kashmir to Sikkim, at Altitudes the Catholic Inquisition, and the Traditional Use of These of up to 2700 Meters
Year of edition: 2018 Authors of the text: Marc Aixalà & José Carlos Bouso Edition: Alex Verdaguer | Genís Oña | Kiko Castellanos Illustrations: Alba Teixidor EU Project: New Approaches in Harm Reduction Policies and Practices (NAHRPP) Special thanks to collaborators Alejandro Ponce (in Peyote report) and Eduardo Carchedi (in Kambó report). TECHNICAL REPORT ON PSYCHOACTIVE ETHNOBOTANICALS Volumes I - II - III ICEERS International Center for Ethnobotanical Education Research and Service INDEX SALVIA DIVINORUM 7 AMANITA MUSCARIA 13 DATURA STRAMONIUM 19 KRATOM 23 PEYOTE 29 BUFO ALVARIUS 37 PSILOCYBIN MUSHROOMS 43 IPOMOEA VIOLACEA 51 AYAHUASCA 57 IBOGA 67 KAMBÓ 73 SAN PEDRO 79 6 SALVIA DIVINORUM SALVIA DIVINORUM The effects of the Hierba Pastora have been used by Mazatec Indians since ancient times to treat diseases and for divinatory purposes. The psychoactive compound Salvia divinorum contains, Salvinorin A, is the most potent naturally occurring psychoactive substance known. BASIC INFO Ska Pastora has been used in divination and healing Salvia divinorum is a perennial plant native to the Maza- rituals, similar to psilocybin mushrooms. Maria Sabina tec areas of the Sierra Madre Oriental Mountains of Mexi- told Wasson and Hofmann (the discoverers of its Mazatec co. Its habitat is tropical forests, where it grows between usage) that Salvia divinorum was used in times when the- 300 and 800 meters above sea level. It belongs to the re was a shortage of mushrooms. Some sources that have Lamiaceae family, and is mainly reproduced by cuttings done later feldwork point out that the use of S. divinorum since it rarely produces seeds. may be more widespread than originally believed, even in times when mushrooms were abundant. -
Ethylene-Induced Vinblastine Accumulation Is Related to Activated Expression of Downstream TIA Pathway Genes in Catharanthus Roseus
Hindawi Publishing Corporation BioMed Research International Volume 2016, Article ID 3708187, 8 pages http://dx.doi.org/10.1155/2016/3708187 Research Article Ethylene-Induced Vinblastine Accumulation Is Related to Activated Expression of Downstream TIA Pathway Genes in Catharanthus roseus Xi Wang,1 Ya-Jie Pan,1 Bo-Wen Chang,2 Yan-Bo Hu,2 Xiao-Rui Guo,1 and Zhong-Hua Tang1 1 Key Laboratory of Forest Plant Ecology, Northeast Forestry University, Harbin 150040, China 2College of Life Science, Northeast Forestry University, Harbin 150040, China Correspondence should be addressed to Xiao-Rui Guo; [email protected] and Zhong-Hua Tang; [email protected] Received 13 December 2015; Revised 30 March 2016; Accepted 6 April 2016 Academic Editor: Sudhir Sopory Copyright © 2016 Xi Wang et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. We selected different concentrations of ethephon, to stress C. roseus.WeusedqRT-PCRandHPLCfollowedbyPCAtoobtain comprehensive profiling of the vinblastine biosynthesis in response to ethephon. Based on our findings, the results showed thatthe high concentration of ethephon had a positive effect at both transcriptional and metabolite level. Meanwhile, there was a remarkable decrease of hydrogen peroxide content and a promoted peroxidase activity in leaves. The loading plot combination with correlation analysis suggested that CrPrx1 could be regarded as a positive regulator and interacts with ethylene response factor (ERF)toplaya key role in vinblastine content and peroxidase (POD) activity. This study provides the foundation for a better understanding of the regulation and accumulation of vinblastine in response to ethephon.