Catharanthus Roseus (L.) G. Don. an Important Drug: Its Applications and Production
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Rhazya Stricta S
IENCE SC • VTT VTT S CIENCE • T S E Alkaloids of in vitro cultures of N C O H I N Rhazya stricta S O I V Dis s e r ta tion L • O S 93 G Rhazya stricta Decne. (Apocynaceae) is a traditional medicinal T Y H • R plant in Middle East and South Asia. It contains a large number of G I E L S H 93 E G terpenoid indole alkaloids (TIAs), some of which possess A I R H C interesting pharmacological properties. This study was focused on H biotechnological production tools of R. stricta, namely undifferentiated cell cultures, and an Agrobacterium rhizogenes- mediated transformation method to obtain hairy roots expressing heterologous genes from the early TIA pathway. Rha zya alkaloids comprise a wide range of structures and polarities, therefore, many A analytical methods were developed to investigate the alkaloid l k contents in in vitro cultures. Targeted and non-targeted analyses a l o were carried out using gas chromatography-mass spectrometry i d (GC-MS), high performance liquid chromatography (HPLC), ultra s o performance liquid chromatography-mass spectrometry (UPLC- f i MS) and nuclear magnetic resonance (NMR) spectroscopy. n Calli derived from stems contained elevated levels of v i t r strictosidine lactam compared to other in vitro cultures. It o was revealed that only leaves were susceptible to Agrobacterium c u infection and subsequent root induction. The transformation l t u efficiency varied from 22% to 83% depending on the gene. A total r e of 17 TIAs were identified from hairy root extracts by UPLC-MS. -
M.Sc. CHEMISTRY
M.Sc. CHEMISTRY ANALYTICAL CHEMISTRY SPECIALISATION SYLLABUS OF III & IV SEMESTERS REVISED AS PER NEW (CB) SYLLABUS FOR STUDENTS ADMITTED FROM THE YEAR 2016 ONWARDS M.Sc. CHEMISTRY (ANALYTICAL CHEMISTRY SPECIALISATION) Syllabus for III and IV Semesters (for the batches admitted in academic year 2016 & later under CBCS pattern) [Under Restructured CBCS Scheme] Grand total marks and credits (all 4 semesters) 2400 marks – 96 credits (Approved in the P.G. BOS meeting held on 01-07-2017) Semester - III (ANALYTICAL CHEMISTRY) [Under CBCS Scheme] (for the batches admitted in academic year 2016 & later under CBCS pattern) Hrs/week Internal assessment Semester exam Total Credits CH(AC)301T (core) 4 20 marks 80 marks 100 marks 4 CH(AC)302T (core) 4 20 marks 80 marks 100 marks 4 CH(AC)303T (Elective) 4 20 marks 80 marks 100 marks 4 CH(AC)304T (Elective) 4 20 marks 80 marks 100 marks 4 CH(AC)351P (LAB-I) 9 100 marks 4 CH(AC)352P (LAB-II) 9 100 marks 4 Total 600 marks 24 Semester - IV (ANALYTICAL CHEMISTRY) Hrs/week Internal assessment Semester exam Total Credits CH(AC)401T (core) 4 20 marks 80 marks 100 marks 4 CH(AC)402T (core) 4 20 marks 80 marks 100 marks 4 CH(AC)403T (Elective) 4 20 marks 80 marks 100 marks 4 CH(AC)404T (Elective) 4 20 marks 80 marks 100 marks 4 CH(AC)451P (LAB-I) 9 100 marks 4 CH(AC)452P (LAB-II) 9 100 marks 4 Total 600 marks 24 Grand total marks and credits (all 4 semesters) 2400 marks - 96 credits M.Sc.ANALYTICAL CHEMISTRY Semester III Paper I :CH (AC) 301T: CORE : Sampling, Data handling, Classical and Atomic spectral methods -
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. -
J.C.S. Perkin I
2308 J.C.S. Perkin I The Biosynthesis of Monoterpenoid lndole Alkaloids from Strictosidine By Naotaka Nagakura, (Mrs.) Martin8 Ruffer, and Meinhart H. Zenk," Lehrstuhl fur Pflanzenphysiologie, Ruhr-Universitat Bochum, D 4630 Bochum, W. Germany The differential incorporation of doubly labelled strictosidine and vincoside into several indole alkaloids belonging to the Corynanthe (3a and 3p series), Aspidosperma, and lboga types in three plant families has been studied, and it has been demonstrated that only strictosidine is incorporated while vincoside is metabolically inert in these plants with regard to alkaloid formation. During the conversion of strictosidine into the 3P-indole alkaloids, the hydrogen atom at the 3-position is lost, while it is retained during the biosynthesis of the 32 alkaloids. The chemical synthesis of [7-3H]secologanin, an important intermediate for further work in the biosynthesis of monoterpenoid alkaloids, is also described. THEfundamental research of Battersby and Arigoni and (S)-3a stereochemistry, is indeed the key intermediate their associates during the past decade has established in the formation of the three classes of monoterpenoid the central role of loganin and secologanin (2) in the indole alkaloids (Asfiidosfierma, Iboga, and Corynanthe) biosynthesis of a multitude of monoterpenoid indole in Catharanthus roseus (syn. Vinca rosea) plants as well alkaloids. Secologanin (2) is the ultimate precursor for as a variety of other species in cell cultures by in vivo the C-9/C-10 non-tryptamine carbon skeleton -
Chapter Two Biomimetic Partial Synthesis Of
CHAPTER TWO BIOMIMETIC PARTIAL SYNTHESIS OF VALPARICINE AND APPARICINE 2.1 Introduction 2.1.1 Alkaloids of Kopsia arborea A total of 62 alkaloids were isolated from the stem-bark and leaves of Kopsia arborea of which 25 are new alkaloids. Among the alkaloids isolated are valparicine (28),26,27 pericine (31),26,28,29 pericidine (32),30,31 arbophylline (33),32 arboricine (34),30,33 arboricinine (35),30,33 arboflorine (36),30,34 arboloscine (37),30,31 and mersicarpine (38).35 14 The compounds of interest to this research are valparicine (28) and pericine (31). Valparicine (28) was isolated from the stem-bark extract of K. arborea in trace amount. It represents the first member of the pericine-type alkaloids, characterized by a 16-22 exocyclic double bond, in which bond-formation has occurred between C-3 and C-7.26 Preliminary tests indicated that valparicine (28) showed strong cytotoxic effects −1 against human KB cells (IC50 < 5 μgmL ). Valparicine (28) was obtained as a colorless oil, with [α]D −40 (c 0.22, CHCl3). The UV spectrum (228 and 297 nm) indicated the presence of an unsubstituted indolenine chromophore. The EIMS of 28 showed a molecular ion at m/z 276, which 13 analyzed for C19H20N2, differing from pericine (31) by loss of two hydrogens. The C NMR spectrum gave a total of 19 carbon resonances (one methyl, five methylenes, seven methines, and six quaternary carbons) in agreement with the molecular formula. In addition to the six carbon resonances readily attributable to the aromatic moiety, and the imine resonance at δC 186.4, two other downfield quaternary resonances were observed at δC 139.2 and 144.6. -
Biosynthesis by in Situ Hybridization (ISH)
Localization of monoterpenoid indole alkaloid (MIA) biosynthesis by in situ hybridization (ISH) By Elizabeth Edmunds, Hons. B.Sc. A Thesis Submitted to the Department of Biotechnology In partial fulfillment of the requirements For the degree of Masters of Science August, 2012 Brock University St. Catha rines, Ontario ©Elizabeth Edmunds, 2012 ii Acknowledgments First and foremost I would like to thank Dr. Vincenzo Deluca for the opportunity to work in his laboratory under his mentorship. I have appreciated the helpful insight that has guided me through the course of this project. I have gained a valuable experience being able to learn from such an established and knowledgeable researcher. Secondly, I would like to thank my committee members Dr. Jeffrey Atkinson and Dr. Heather Gordon for their support and advice and their time to serve on my advisory committee. Thirdly, I would like to thank my colleagues and co-workers for their patience and helpful advice throughout my project. Particular mention must be given to Dr. Carlone's lab for their assistance and insight into in situ hybridization techniques. Finally, I would like to express my sincerest gratitude and appreciation towards my family and friends for their support. I would not be where I am today without the support and love from my mother and father, as well as Craig Easton. iii Abstract Monoterpenoid indole alkaloids (MIA) are among the largest and most complex group of nitrogen containing secondary metabolites that are characteristic of the Apocynaceae plant family including the most notable Catharanthus roseus. These compounds have demonstrated activity as successful drugs for treating various cancers, neurological disorders and cardiovascular conditions. -
Deploying Microbial Synthesis for Halogenating and Diversifying Medicinal Alkaloid Scaffolds
Downloaded from orbit.dtu.dk on: Sep 28, 2021 Deploying Microbial Synthesis for Halogenating and Diversifying Medicinal Alkaloid Scaffolds Bradley, Samuel Alan; Zhang, Jie; Jensen, Michael Krogh Published in: Frontiers in Bioengineering and Biotechnology Link to article, DOI: 10.3389/fbioe.2020.594126 Publication date: 2020 Document Version Publisher's PDF, also known as Version of record Link back to DTU Orbit Citation (APA): Bradley, S. A., Zhang, J., & Jensen, M. K. (2020). Deploying Microbial Synthesis for Halogenating and Diversifying Medicinal Alkaloid Scaffolds. Frontiers in Bioengineering and Biotechnology, 8, [594126]. https://doi.org/10.3389/fbioe.2020.594126 General rights Copyright and moral rights for the publications made accessible in the public portal are retained by the authors and/or other copyright owners and it is a condition of accessing publications that users recognise and abide by the legal requirements associated with these rights. Users may download and print one copy of any publication from the public portal for the purpose of private study or research. You may not further distribute the material or use it for any profit-making activity or commercial gain You may freely distribute the URL identifying the publication in the public portal If you believe that this document breaches copyright please contact us providing details, and we will remove access to the work immediately and investigate your claim. fbioe-08-594126 October 19, 2020 Time: 19:15 # 1 REVIEW published: 23 October 2020 doi: 10.3389/fbioe.2020.594126 Deploying Microbial Synthesis for Halogenating and Diversifying Medicinal Alkaloid Scaffolds Samuel A. Bradley, Jie Zhang and Michael K. -
Unlocking the Diversity of Alkaloids in Catharanthus Roseus: Nuclear Localization Suggests Metabolic Channeling in Secondary Metabolism
Brief Communication Unlocking the Diversity of Alkaloids in Catharanthus roseus: Nuclear Localization Suggests Metabolic Channeling in Secondary Metabolism Graphical Abstract Authors Anna Stavrinides, Evangelos C. Tatsis, ..., Vincent Courdavault, Sarah E. O’Connor Correspondence [email protected] (S.E.O.), [email protected] (V.C.) In Brief How plants transform the central biosynthetic intermediate strictosidine into thousands of divergent alkaloids has remained unresolved. Stavrinides et al. discover a nuclear-localized alcohol dehydrogenase homolog responsible for conversion of strictosidine aglycone to tetrahydroalstonine that appears to interact with an upstream pathway enzyme. Highlights d Tetrahydroalstonine synthase catalyzes the formation of a plant-derived alkaloid d Tetrahydroalstonine synthase is localized to the nucleus d Tetrahydroalstonine synthase and the preceding pathway enzyme interact d Discovery of a gene controlling structural diversity of monoterpene indole alkaloids Stavrinides et al., 2015, Chemistry & Biology 22, 336–341 March 19, 2015 ª2015 The Authors http://dx.doi.org/10.1016/j.chembiol.2015.02.006 Chemistry & Biology Brief Communication Unlocking the Diversity of Alkaloids in Catharanthus roseus: Nuclear Localization Suggests Metabolic Channeling in Secondary Metabolism Anna Stavrinides,1 Evangelos C. Tatsis,1 Emilien Foureau,2 Lorenzo Caputi,1 Franziska Kellner,1 Vincent Courdavault,2,* and Sarah E. O’Connor1,* 1Department of Biological Chemistry, The John Innes Centre, Colney, Norwich NR4 7UH, UK 2Universite´ Franc¸ ois Rabelais de Tours, EA2106 ‘‘Biomole´ cules et Biotechnologies Ve´ ge´ tales’’, 37200 Tours, France *Correspondence: [email protected] (S.E.O.), [email protected] (V.C.) http://dx.doi.org/10.1016/j.chembiol.2015.02.006 This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). -
Fifty Years of Alkaloid Biosynthesis in Phytochemistry Q ⇑ Geoffrey A
Phytochemistry 91 (2013) 29–51 Contents lists available at SciVerse ScienceDirect Phytochemistry journal homepage: www.elsevier.com/locate/phytochem Review Fifty years of alkaloid biosynthesis in Phytochemistry q ⇑ Geoffrey A. Cordell Natural Products Inc., Evanston, IL, USA Department of Pharmaceutics, College of Pharmacy, University of Florida, Gainesville, FL 32610, USA article info abstract Article history: An overview is presented of the studies related to the biosynthesis of alkaloids published in Phytochem- Available online 20 June 2012 istry in the past 50 years. Ó 2012 Elsevier Ltd. All rights reserved. Keywords: Alkaloids Biosynthesis Overview Contents 1. Introduction . ....................................................................................................... 30 1.1. Ornithine-derived alkaloids . .......................................................................... 30 1.2. Nicotine . .......................................................................................... 31 1.3. Tropane alkaloids . .......................................................................................... 33 1.4. Calystegines . .......................................................................................... 34 1.5. Pyrrolizidine alkaloids. .......................................................................................... 34 1.6. Retronecine . .......................................................................................... 34 1.7. Lysine-derived alkaloids . ......................................................................................... -
Studies on the Synthesis and Biosynthesis Of
STUDIES ON THE SYNTHESIS AND BIOSYNTHESIS OF INDOLE ALKALOIDS BY GEORGE BOHN FULLER B.A. (cum laude) , Macalester College, 1969 M.Sc, The University of California, Berkeley, 19 A THESIS SUBMITTED IN PARTIAL FULFILMENT OF THE REQUIREMENTS FOR THE DEGREE OF DOCTOR OF PHILOSOPHY in the Department of CHEMISTRY We accept this thesis as conforming to the required standard /-) THE UNIVERSITY OF BRITISH COLUMBIA July, 1974 In presenting this thesis in partial fulfilment of the requirements for an advanced degree at the University of British Columbia, I agree that the Library shall make it freely available for reference and study. I further agree that permission for extensive copying of this thesis for scholarly purposes may be granted by the Head of my Department or by his representatives. It is understood that copying or publication of this thesis for financial gain shall not be allowed without my written permission. Depa rtment The University of British Columbia Vancouver 8, Canada ABSTRACT Part A of this thesis provides a resume1 of the synthesis of various radioactively labelled forms of secodine C76) and provides an evaluation of these compounds, as well as some radioactively labelled forms of tryptophan C25), as precursors in the Biosynthesis of apparicine (81), uleine C83), guatam- buine (90) , and olivacine (88) in Aspidosperma australe. Only apparicine (81) could be shown to incorporate these precursors to a significant extent. Degradation of apparicine (81) from Aspidosperma pyricollum provided evidence for the intact incorporation of the secodine system. Part B discusses the synthesis of 16-epi-stemmadenine (161), which provides an entry into the stemmadenine system with, radioactive labels at key positions in the molecule. -
Solution of the Multistep Pathway for Assembly of Corynanthean, Strychnos, Iboga, and Aspidosperma Monoterpenoid Indole Alkaloids from 19E-Geissoschizine
Solution of the multistep pathway for assembly of corynanthean, strychnos, iboga, and aspidosperma monoterpenoid indole alkaloids from 19E-geissoschizine Yang Qua, Michael E. A. M. Eassona,1, Razvan Simionescub, Josef Hajicekb,2, Antje M. K. Thamma,3, Vonny Salima,4, and Vincenzo De Lucaa,5 aDepartment of Biological Sciences, Brock University, St. Catharines, ON L2S 3A1, Canada; and bDepartment of Chemistry, Brock University, St. Catharines, ON L2S 3A1, Canada Edited by Jerrold Meinwald, Cornell University, Ithaca, NY, and approved February 11, 2018 (received for review November 16, 2017) Monoterpenoid indole alkaloids (MIAs) possess a diversity of for the formation of tabersonine or catharanthine from 19E- alkaloid skeletons whose biosynthesis is poorly understood. A geissoschizine. Gene discovery involved a combination of bio- bioinformatic search of candidate genes, combined with their informatics and virus-induced gene silencing (VIGS) to identify virus-induced gene silencing, targeted MIA profiling and in vitro/ candidate genes and functional expression of the selected genes in vivo pathway reconstitution identified and functionally charac- by in vitro/in vivo reconstitution of the pathway. A series of terized six genes as well as a seventh enzyme reaction required for highly unstable intermediates that rearrange to other important the conversion of 19E-geissoschizine to tabersonine and catharan- MIA precursors when not used by appropriate enzymes reveals thine. The involvement of pathway intermediates in the formation the plasticity of MIA formation and how this fundamental of four MIA skeletons is described, and the role of stemmadenine- property led to diverse MIA structures found in nature. O-acetylation in providing necessary reactive substrates for the formation of iboga and aspidosperma MIAs is described. -
Total Synthesis of the Bridged Indole Alkaloid Apparicine
pubs.acs.org/joc Total Synthesis of the Bridged Indole Alkaloid Apparicine M.-Lluı¨ sa Bennasar,* Ester Zulaica, Daniel Sole, Tomas Roca, Davinia Garcı´ a-Dı´ az, and Sandra Alonso Laboratory of Organic Chemistry, Faculty of Pharmacy, and Institut de Biomedicina (IBUB), University of Barcelona, Barcelona 08028, Spain [email protected] Received September 15, 2009 An indole-templated ring-closing metathesis or a 2-indolylacyl radical cyclization constitute the central steps of two alternative approaches developed to assemble the tricyclic ABC substructure of the indole alkaloid apparicine. From this key intermediate, an intramolecular vinyl halide Heck reaction accomplished the closure of the strained 1-azabicyclo[4.2.2]decane framework of the alkaloid with concomitant incorporation of the exocyclic alkylidene substituents. Introduction Apparicine (Figure 1) is a fairly widespread monoterpenoid indole alkaloid, first isolated from Aspidosperma dasycarpon more than 40 years ago.1,2 Its structural elucidation,2 carried out by chemical degradation and early spectroscopic techni- ques, revealed a particular skeleton with a bridged 1-azabi- cyclo[4.2.2]decane framework fused to the indole ring and two exocyclic alkylidene (16-methylene and 20E-ethylidene) sub- Publication Date (Web): October 14, 2009 | doi: 10.1021/jo901986v stituents.3 Thesamearrangementwasalsofoundinvallesa- mine4 and later in a small number of alkaloids, including 16(S)- 5 6 Downloaded by UNIV OF BARCELONA on October 20, 2009 | http://pubs.acs.org hydroxy-16,22-dihydroapparicine or ervaticine, which differ from apparicine in the substitution at C-16.7 The apparicine alkaloids are biogenetically defined by the presence of only one carbon (C-6) connecting the indole 3- position and the aliphatic nitrogen, which is the result of the C-5 (1) Gilbert, B.; Duarte, A.