DOCSLIB.ORG

Studies Toward a General Synthesis of Poly-Substituted Alpha- Hydroxytropolones

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Studies Toward a General Synthesis of Poly-Substituted Alpha- Hydroxytropolones City University of New York (CUNY) CUNY Academic Works All Dissertations, Theses, and Capstone Projects Dissertations, Theses, and Capstone Projects 9-2015 Studies Toward a General Synthesis of Poly-Substituted Alpha- Hydroxytropolones Christine Marie Meck Graduate Center, City University of New York How does access to this work benefit ou?y Let us know! More information about this work at: https://academicworks.cuny.edu/gc_etds/1050 Discover additional works at: https://academicworks.cuny.edu This work is made publicly available by the City University of New York (CUNY). Contact: [email protected] Studies Toward a General Synthesis of Poly-Substituted Alpha-Hydroxytropolones by Christine Meck A dissertation submitted to the Graduate Faculty in Chemistry in partial fulfillment of the requirements for the degree of Doctor of Philosophy, The City University of New York 2015 © 2015 CHRISTINE MECK All Rights Reserved ii This manuscript has been read and accepted for the Graduate Faculty in Chemistry in satisfaction of the dissertation requirement for the degree of Doctor of Philosophy. Prof. Ryan P. Murelli, Ph.D ____________________ ________________________________ Date Chair of Examining Committee Prof. Brian Gibney, Ph.D. ____________________ ________________________________ Date Executive Officer Prof. Maria Contel, Ph.D. ________________________________ Prof. Shengping Zheng, Ph.D. ________________________________ Supervisory Committee THE CITY UNIVERSITY OF NEW YORK iii ABSTRACT Studies Toward a General Synthesis of Poly-Substituted Alpha-Hydroxytropolones by Christine Meck Advisor: Prof. Ryan P. Murelli, Ph.D. Chapter 1: This chapter gives a brief history of α-hydroxytropolones, how they were discovered and unique properties of these substrates. Included is a background on the bioactivity of these substrates in cellular targets such as bacteria, fungi, parasites, tumors and toxicity, as well as their ability to inhibit various metallo-based enzymes. Structure activity relationships studies are reviewed on important metalloenzymes HIV-Reverse Transcriptase (RT) and Inositol monophosphatase (IMPase). Finally the chapter finishes with a synthetic overview of α-hydroxytropolones including natural product targets such as puberulic acid, puberulonic acid, β-thujaplicinol, and α-hydroxytropolone. Chapter 2: A brief review on β-hydroxy-γ-pyrone based oxidopyrylium cycloadditions will be presented as well as important oxidopyrylium cycloaddition/ring opening procedures to yield natural tropolone products. Research from the Murelli laboratory will be highlighted. This chapter will discuss a new synthetic route toward functionalized α-hydroxytropolones. A β-hydroxy-γ-pyrone intermolecular oxidopyrylium cycloaddition with a range of alkynes that was optimized to an efficient and high yielding process will be discussed. Next two ring catalyzed ring openings will be discussed; one that utilizes boron trichloride that attains α-hydroxytropolones and 7-methoxytropolones, and a triflic acid mediated sequence that yields exclusive 7-methoyxtropolones and furans. Finally, a new reaction with the oxidopyrylium species will be highlighted that shows the exchange of alcohols in these reactive species. iv Chapter 3: Chapter three describes the background on three specific medicinal targets: ANT (2”)-Ia, HIV RT RNase H, and HBV RT RNaseH and preliminary structure activity relationship studies with α- hydroxytropolones synthesized in this research are outlined. v ACKNOWLEDGEMENTS The journey of my Ph.D. was somewhat of surprise for me. At 22 years old I got married and graduated college with a degree in English literature. I could have never imagined at 32 years old and two children later, I would be graduating with a Ph.D. in chemistry. I truly believe God’s hand was at work by placing important people and circumstances in my life to bring me to this point. First, I want to thank the chemistry faculty and staff at Brooklyn College and the Graduate Center. They created a consistently positive environment and constant support system. I want to thank my Committee Members, my former member Dr. Stacey Brenner-Moyer who pushed me to pursue the Ph.D. while aligning me with my research mentor Ryan Murelli. Maria Contel who showed me a strong confident woman scientist that inspired me to feel confident in my own abilities. Shengping Zheng whose synthesis class really engrained organic chemistry in mind and who always pushed me mentally. Second, a seminal figure in my journey was my mentor Ryan Murelli. I remember first talking on the phone with Ryan about his research and joining his group before he even started. I think we both were unsure what we were getting into, but we trusted each other, and that trust led to a productive and successful relationship. He really taught me chemistry, made chemistry fun and exciting, and pushed me to be the best chemist that I could be. He believed in me no matter what, and his positive spirit helped me to overcome barriers in my life and research. I will always be grateful for him for supporting my family life, which took a great burden off my chest, and helped me to continue to finish my Ph.D. Third, I want to thank Bonnie Kruft, Ashwini Ghogare, Rico Fraboni, Josh Jones, and Goshia Frik, who have become friends for life. They have made this Ph.D. experience enjoyable and bearable. I am so grateful to have crossed paths with these amazing individuals. I want to thank my lab mates Noushad Mohd, Danielle Hirsch, Mike D’Erasmo, and Yvonne Williams for making the lab environment like a home and for their constant support in our chemistry endeavors. I want to thank Noushad Mohd for his assistance on many of the projects. His energy and dedication was an important part in the development of this chemistry. vi Next, I want to thank my mom and dad for always supporting me no matter what I wanted to do in life. They always made sure I had lots of love. My mother, as a single parent, taught me strength, courage, and hard work. Also I want to thank my grandmother Carol Signore for her teachings, love, and always being a constant force in my life. I want to give a special thank you to my mother-in-law Marilyn Allen. She sacrificed her life and time to take care of an infant during some of the toughest months, while I finished work towards my Ph.D. I will always remember this selfless act. Finally, my husband of 10 years Bill Allen deserves more praise then my words can express. He encouraged me to stick with the Ph.D. when many times I just wanted to quit. I saw his love for me as he sacrificed his time to solely take care of the boys while I worked on my thesis. He took care of our son while I was gone for a week at a time in the city to finish my research, and wanted my success in life more than his own. He is not only handsome on the outside, but inside he is truly beautiful and godly, and every day I thank God for letting us find each other in this life. He is an awesome father, husband, friend, and he is the love of my life. I want to give praise to God for his guidance on this path. Not only did I grow spiritually through this journey, but he showed me what it meant to trust him. He blessed me with my two boys, L.D. and J.D. whose presence in my life continually motivates me to do it all for them. Also I want to thank our collaborators John Tavis, John Beutler and Staurt Le Grice, and Gerry Wright. Dr. Chad Lewis and the Lewis group at Cornell for hosting me for a summer and being for gracious, supportive, and helpful. I want to thank Connie Davis for our MS data and William W. Brennessel for crystal data. Also this research would not have been possible without funding from the NIH Score Grant (SC2GM099596) and PSC CUNY (65420-00-43), Brooklyn College, and the Graduate Center. vii TABLE OF CONTENTS 1. Chapter 1: The Biology and Synthesis of α-Hydroxytropolones ................................. 1 1.1 Introduction: A Short History and Background on α-Hydroxytropolones ..... 1 1.2 Cytotoxicity of α-Hydroxytropolones ................................................................. 2 1.2.1 Antifungal Activity ...................................................................................... 2 1.2.2 Antibacterial Activity ................................................................................... 3 1.2.3 Antitumor Activity ...................................................................................... 4 1.2.4 Antimalarial Activity ................................................................................... 5 1.2.5 Toxicology Studies .................................................................................... 6 1.3 Metalloenzyme Inhibition ................................................................................... 7 1.3.1 Inositol Monophosphatase (IMPase) ........................................................ 7 1.3.2 Aminoglycoside 2”-O-adenylyltransferase [ANT(2”)] ................................ 9 1.3.3 HIV (Human Immunodeficiency Virus) Reverse Transcriptase (RT): The Ribonuclease H (RNASE H) Active Site .............................................................. 11 1.3.4 Xenotropic Murine Leukemia Virus Related Virus (XMRV) and Herpes Simple Virus (HSV) ................................................................................. 13 1.3.5 Hepatitis B Virus (HBV) RNase H ........................................................... 14 1.3.6 Phosphotidylcholine-Preferring Phospholipase C ................................... 15 1.4 Structure Activity Relationship Studies
Load more

Recommended publications
  • Transfer of Pseudomonas Plantarii and Pseudomonas Glumae to Burkholderia As Burkholderia Spp
    INTERNATIONALJOURNAL OF SYSTEMATICBACTERIOLOGY, Apr. 1994, p. 235-245 Vol. 44, No. 2 0020-7713/94/$04.00+0 Copyright 0 1994, International Union of Microbiological Societies Transfer of Pseudomonas plantarii and Pseudomonas glumae to Burkholderia as Burkholderia spp. and Description of Burkholderia vandii sp. nov. TEIZI URAKAMI, ’ * CHIEKO ITO-YOSHIDA,’ HISAYA ARAKI,’ TOSHIO KIJIMA,3 KEN-ICHIRO SUZUKI,4 AND MU0KOMAGATA’T Biochemicals Division, Mitsubishi Gas Chemical Co., Shibaura, Minato-ku, Tokyo 105, Niigata Research Laboratory, Mitsubishi Gas Chemical Co., Tayuhama, Niigatu 950-31, ’Plant Pathological Division of Biotechnology, Tochigi Agricultural Experiment Station, Utsunomiya 320, Japan Collection of Microorganisms, The Institute of Physical and Chemical Research, Wako-shi, Saitama 351-01,4 and Institute of Molecular Cell and Biology, The University of Tokyo, Bunkyo-ku, Tokyo 113,’ Japan Plant-associated bacteria were characterized and are discussed in relation to authentic members of the genus Pseudomonas sensu stricto. Bacteria belonging to Pseudomonas rRNA group I1 are separated clearly from members of the genus Pseudomonas sensu stricto (Pseudomonasfluorescens rRNA group) on the basis of plant association characteristics, chemotaxonomic characteristics, DNA-DNA hybridization data, rRNA-DNA hy- bridization data, and the sequences of 5s and 16s rRNAs. The transfer of Pseudomonas cepacia, Pseudomonas mallei, Pseudomonas pseudomallei, Pseudomonas caryophylli, Pseudomonas gladioli, Pseudomonas pickettii, and Pseudomonas solanacearum to the new genus Burkholderia is supported; we also propose that Pseudomonas plantarii and Pseudomonas glumae should be transferred to the genus Burkholderia. Isolate VA-1316T (T = type strain) was distinguished from Burkholderia species on the basis of physiological characteristics and DNA-DNA hybridization data. A new species, Burkholderia vandii sp.
    [Show full text]
  • Medical Botany 6: Active Compounds, Continued- Safety, Regulations
    Medical Botany 6: Active compounds, continued- safety, regulations Anthocyanins / Anthocyanins (Table 5I) O Anthocyanidins (such as malvidin, cyanidin), agrocons of anthocyanins (such as malvidin 3-O- glucoside, cyanidin 3-O-glycoside). O All carry cyanide main structure (aromatic structure). ▪ Introducing or removing the hydroxyl group (-OH) from the structure, The methylation of the structure (-OCH3, methoxyl group), etc. reactants and color materials are shaped. It is commonly found in plants (plant sap). O Flowers, leaves, fruits give their colors (purple, red, red, lilac, blue, purple, pink). O The plant's color is related to the pH of the cell extract. O Red color anthocyanins are blue, blue-purple in alkaline conditions. O Effects of many factors in color As the pH increases, the color becomes blue. the phenyl ring attached to C2; • As the OH number increases, the color becomes blue, • color increases as the methoxyl group increases. O Combination of flavonoids and anthocyanins produces blue shades. There are 6 anthocyanidins, more prevalent among ornamental-red. 3 of them are hydroxylated (delfinine, pelargonidine, cyanidin), 3 are methoxylated (malvidin, peonidin, petunidin). • Orange-colored pelargonidin related. O A hydroxyl group from cyanide contains less. • Lilac, purple, blue color is related to delphinidin. It contains a hydroxyl group more than cyanide. • Three anthocyanidines are common in methyl ether; From these; Peonidine; Cyanide, Malvidin and petunidin; Lt; / RTI & gt; derivative. O They help to pollinize animals for what they are attracted to. Anthocyanins and anthocyanidins are generally anti-inflammatory, cell and tissue protective in mammals. O Catches and removes active oxygen groups (such as O2 * -, HO *) and prevents oxidation.
    [Show full text]
  • Caomatograpby
    rOURNAL DF LIQUID CaOMATOGRAPBY VOLUME 18 NUMBER 7 1995 ~ditor: DR. JACK CAZES ~ssociate Editors: DR. HALEEM J. ISSAQ DR. STEVEN H. WONG Special Section on CAPILlARY ZONE ELECTROPHORESIS AND REIATED TECHNIQUES Edited by HALEEM J. ISSAQ NCI-Frederick Cancer Research & Development Center Frederick, Maryland JOURNAL OF LIQUID CHROMATOGRAPHY April 1995 Aims and Scope. The journal publishes papers involving the applications of liquid chromatography to the solution of problems in all areas of science and technology, both analytical and preparative, as well as papers that deal specifically with liquid chromatography as a science within itself. Included will be thin-layer chromatography and all models of liquid chromatography. IdentiilCation Statement. Journal of Liquid Chromatography (lSSN: 0148-3919) is published semimonthly except monthly in May, August, October, and December for the institutional rate of $1,450.00 and the individual rate of $725.00 by Marcel Dekker, Inc., P.O. Box 5005, Monticello, NY 12701-5185. Second Class postage paid at Monticello, NY. POSTMASTER: Send address changes to Journal ofLiquid Chromatography, P.O. Box 5005, Monticello, NY 12701-5185. Individual Foreign Postage Professionals' Institutional and Student Airmail Airmail Volume Issues Rate Rate Surface to Europe to Asia 18 20 $1,450.00 $725.00 $70.00 $110.00 $130.00 Individual professionals' and student orders must be prepaid by personal check or may be charged to MasterCard, VISA, or American Express. Please mail payment with your order to: Marcel Dekker Journals, P.O. Box 5017, Monticello, New York 12701-5176. CODEN: JLCHD8 18(7) i-iv, 1273-1494 (1995) ISSN: 0148-3919 Printed in the U.S.A.
    [Show full text]
  • Understanding Drug-Drug Interactions Due to Mechanism-Based Inhibition in Clinical Practice
    pharmaceutics Review Mechanisms of CYP450 Inhibition: Understanding Drug-Drug Interactions Due to Mechanism-Based Inhibition in Clinical Practice Malavika Deodhar 1, Sweilem B Al Rihani 1 , Meghan J. Arwood 1, Lucy Darakjian 1, Pamela Dow 1 , Jacques Turgeon 1,2 and Veronique Michaud 1,2,* 1 Tabula Rasa HealthCare Precision Pharmacotherapy Research and Development Institute, Orlando, FL 32827, USA; [email protected] (M.D.); [email protected] (S.B.A.R.); [email protected] (M.J.A.); [email protected] (L.D.); [email protected] (P.D.); [email protected] (J.T.) 2 Faculty of Pharmacy, Université de Montréal, Montreal, QC H3C 3J7, Canada * Correspondence: [email protected]; Tel.: +1-856-938-8697 Received: 5 August 2020; Accepted: 31 August 2020; Published: 4 September 2020 Abstract: In an ageing society, polypharmacy has become a major public health and economic issue. Overuse of medications, especially in patients with chronic diseases, carries major health risks. One common consequence of polypharmacy is the increased emergence of adverse drug events, mainly from drug–drug interactions. The majority of currently available drugs are metabolized by CYP450 enzymes. Interactions due to shared CYP450-mediated metabolic pathways for two or more drugs are frequent, especially through reversible or irreversible CYP450 inhibition. The magnitude of these interactions depends on several factors, including varying affinity and concentration of substrates, time delay between the administration of the drugs, and mechanisms of CYP450 inhibition. Various types of CYP450 inhibition (competitive, non-competitive, mechanism-based) have been observed clinically, and interactions of these types require a distinct clinical management strategy. This review focuses on mechanism-based inhibition, which occurs when a substrate forms a reactive intermediate, creating a stable enzyme–intermediate complex that irreversibly reduces enzyme activity.
    [Show full text]
  • United States Patent (19) [11] Patent Number: 5,658,584 Yamaguchi 45) Date of Patent: Aug
    US005658584A United States Patent (19) [11] Patent Number: 5,658,584 Yamaguchi 45) Date of Patent: Aug. 19, 1997 54 ANTIMICROBIAL COMPOSITIONS WITH 2-243607 9/1990 Japan ............................. AON 37/10 HNOKTOL AND CTRONELLCACD 4-182408 6/1992 Japan ............................. A01N 6500 5-271073 10/1993 Japan ............................. A61K 31/40 75 Inventor: Yuzo Yamaguchi, Kanagawa, Japan OTHER PUBLICATIONS 73) Assignee: Takasago international Corporation, Tokyo, Japan ROKURO, World Patent Abstract of JP 6048936, Feb. 1994. Osada et al., Patent Abstracts of Japan, JP 3077801, 1991. 21 Appl. No.: 513,181 Osamu Okuda, Koryo Kagaku Soran (Fragrance Chemistry 22 Filed: Aug. 9, 1995 Comprehensive Bibliography) (II), published by Hirokawa Shoten, (1963) p. 1140. (30) Foreign Application Priority Data Yuzo Yamaguchi, Fragrance Journal, No. 46, (1981) Aug. 19, 1994 JP Japan .................................... 6-216686 (Japan) pp. 56-59. (51] Int. Cl. .............. A01N 25/00; A01N 25/06; A01N 25/02; A01N 25/08 Primary Examiner-Edward J. Webman (52) U.S. Cl. ......................... 424/405; 424/404; 424/408; Attorney, Agent, or Firm-Sughrue, Mion, Zinn, Macpeak 424/410; 424/414 & Seas 58 Field of Search ................................. 424/400, 405, 57 ABSTRACT 424/45, 408, 414, 410, 404 An antimicrobial composition containing a mixture of hino 56) References Cited kitiol and citronellic acid in a ratio of about 1:1 to about 3:1 by weight. The antimicrobial composition according to the U.S. PATENT DOCUMENTS invention is safe for humans and has a high antimicrobial 4,645,536 2/1987 Butler ................................... 106/15.05 activity and a broad antimicrobial spectrum, and is widely 5,053,222 10/1991 Takasu et al.
    [Show full text]
  • Journal of Inorganic Biochemistry 187 (2018) 73–84
    Journal of Inorganic Biochemistry 187 (2018) 73–84 Contents lists available at ScienceDirect Journal of Inorganic Biochemistry journal homepage: www.elsevier.com/locate/jinorgbio New heterobimetallic ferrocenyl derivatives: Evaluation of their potential as prospective agents against trypanosomatid parasites and Mycobacterium T tuberculosis Feriannys Rivasa, Andrea Medeirosb,c, Esteban Rodríguez Arcea, Marcelo Cominib, ⁎ Camila M. Ribeirod, Fernando R. Pavand, Dinorah Gambinoa, a Área Química Inorgánica, Facultad de Química, Universidad de la República, Montevideo, Uruguay b Group Redox Biology of Trypanosomes, Institut Pasteur Montevideo, Montevideo, Uruguay c Departamento de Bioquímica, Facultad de Medicina, Universidad de la República, Montevideo, Uruguay d Faculdade de Ciências Farmacêuticas, UNESP, Araraquara, Brazil ARTICLE INFO ABSTRACT Keywords: Searching for prospective agents against infectious diseases, four new ferrocenyl derivatives, [M(L)(dppf)4] Ferrocenyl compounds (PF6), with M = Pd(II) or Pt(II), dppf = 1,1′-bis(dipheny1phosphino) ferrocene and HL = tropolone (HTrop) or Tropolone derivatives hinokitiol (HHino), were synthesized and characterized. Complexes and ligands were evaluated against the Trypanosoma brucei bloodstream form of T. brucei, L. infantum amastigotes, M. tuberculosis (MTB) sensitive strain and MTB clinical Mycobacterium tuberculosis isolates. Complexes showed a significant increase of the anti-T. brucei activity with respect to the free ligands Leishmaniasis (> 28- and > 46-fold for Trop and 6- and 22-fold for Hino coordinated to Pt-dppf and Pd-dppf, respectively), yielding IC50 values < 5 μM. The complexes proved to be more potent than the antitrypanosomal drug Nifurtimox. The new ferrocenyl derivatives were more selective towards the parasite than the free ligands. The Pt compounds were less toxic on J774 murine macrophages (mammalian cell model), than the Pd ones, showing selectivity index values (SI = IC50 murine macrophage/IC50 T.
    [Show full text]
  • Effect of Thujaplicins on the Promoter Activities of the Human SIRT1 And
    A tica nal eu yt c ic a a m A r a c t Uchiumi et al., Pharmaceut Anal Acta 2012, 3:5 h a P DOI: 10.4172/2153-2435.1000159 ISSN: 2153-2435 Pharmaceutica Analytica Acta Research Article Open Access Effects of Thujaplicins on the Promoter Activities of the Human SIRT1 and Telomere Maintenance Factor Encoding Genes Fumiaki Uchiumi1,2, Haruki Tachibana3, Hideaki Abe4, Atsushi Yoshimori5, Takanori Kamiya4, Makoto Fujikawa3, Steven Larsen2, Asuka Honma4, Shigeo Ebizuka4 and Sei-ichi Tanuma2,3,6,7* 1Department of Gene Regulation, Faculty of Pharmaceutical Sciences, Tokyo University of Science, Noda-shi, Chiba-ken 278-8510, Japan 2Research Center for RNA Science, RIST, Tokyo University of Science, Noda-shi, Chiba-ken, Japan 3Department of Biochemistry, Faculty of Pharmaceutical Sciences, Tokyo University of Science, Noda-shi, Chiba-ken 278-8510, Japan 4Hinoki Shinyaku Co., Ltd, 9-6 Nibancho, Chiyoda-ku, Tokyo 102-0084, Japan 5Institute for Theoretical Medicine, Inc., 4259-3 Nagatsuda-cho, Midori-ku, Yokohama 226-8510, Japan 6Genome and Drug Research Center, Tokyo University of Science, Noda-shi, Chiba-ken 278-8510, Japan 7Drug Creation Frontier Research Center, RIST, Tokyo University of Science, Noda-shi, Chiba-ken 278-8510, Japan Abstract Resveratrol (Rsv) has been shown to extend the lifespan of diverse range of species to activate sirtuin (SIRT) family proteins, which belong to the class III NAD+ dependent histone de-acetylases (HDACs).The protein de- acetylating enzyme SIRT1 has been implicated in the regulation of cellular senescence and aging processes in mammalian cells. However, higher concentrations of this natural compound cause cell death.
    [Show full text]
  • (12) United States Patent (10) Patent No.: US 9,636.405 B2 Tamarkin Et Al
    USOO9636405B2 (12) United States Patent (10) Patent No.: US 9,636.405 B2 Tamarkin et al. (45) Date of Patent: May 2, 2017 (54) FOAMABLE VEHICLE AND (56) References Cited PHARMACEUTICAL COMPOSITIONS U.S. PATENT DOCUMENTS THEREOF M (71) Applicant: Foamix Pharmaceuticals Ltd., 1,159,250 A 1 1/1915 Moulton Rehovot (IL) 1,666,684 A 4, 1928 Carstens 1924,972 A 8, 1933 Beckert (72) Inventors: Dov Tamarkin, Maccabim (IL); Doron 2,085,733. A T. 1937 Bird Friedman, Karmei Yosef (IL); Meir 33 A 1683 Sk Eini, Ness Ziona (IL); Alex Besonov, 2,586.287- 4 A 2/1952 AppersonO Rehovot (IL) 2,617,754. A 1 1/1952 Neely 2,767,712 A 10, 1956 Waterman (73) Assignee: EMY PHARMACEUTICALs 2.968,628 A 1/1961 Reed ... Rehovot (IL) 3,004,894. A 10/1961 Johnson et al. (*) Notice: Subject to any disclaimer, the term of this 3,062,715. A 1 1/1962 Reese et al. tent is extended or adiusted under 35 3,067,784. A 12/1962 Gorman pa 3,092.255. A 6/1963 Hohman U.S.C. 154(b) by 37 days. 3,092,555 A 6/1963 Horn 3,141,821 A 7, 1964 Compeau (21) Appl. No.: 13/793,893 3,142,420 A 7/1964 Gawthrop (22) Filed: Mar. 11, 2013 3,144,386 A 8/1964 Brightenback O O 3,149,543 A 9/1964 Naab (65) Prior Publication Data 3,154,075 A 10, 1964 Weckesser US 2013/0189193 A1 Jul 25, 2013 3,178,352.
    [Show full text]
  • Smell and Stress Response in the Brain: Review of the Connection Between Chemistry and Neuropharmacology
    molecules Review Smell and Stress Response in the Brain: Review of the Connection between Chemistry and Neuropharmacology Yoshinori Masuo 1,*, Tadaaki Satou 2 , Hiroaki Takemoto 3 and Kazuo Koike 3 1 Laboratory of Neuroscience, Department of Biology, Faculty of Science, Toho University, 2-2-1 Miyama, Funabashi, Chiba 274-8510, Japan 2 Department of Pharmacognosy, Faculty of Pharmaceutical Sciences, International University of Health and Welfare, 2600-1 Kitakanemaru, Ohtawara, Tochigi 324-8501, Japan; [email protected] 3 Department of Pharmacognosy, Faculty of Pharmaceutical Sciences, Toho University, 2-2-1 Miyama, Funabashi, Chiba 274-8510, Japan; [email protected] (H.T.); [email protected] (K.K.) * Correspondence: [email protected]; Tel.: +81-47-472-5257 Abstract: The stress response in the brain is not fully understood, although stress is one of the risk factors for developing mental disorders. On the other hand, the stimulation of the olfactory system can influence stress levels, and a certain smell has been empirically known to have a stress- suppressing effect, indeed. In this review, we first outline what stress is and previous studies on stress-responsive biomarkers (stress markers) in the brain. Subsequently, we confirm the olfactory system and review previous studies on the relationship between smell and stress response by species, such as humans, rats, and mice. Numerous studies demonstrated the stress-suppressing effects of aroma. There are also investigations showing the effects of odor that induce stress in experimental animals. In addition, we introduce recent studies on the effects of aroma of coffee beans and essential oils, such as lavender, cypress, α-pinene, and thyme linalool on the behavior and the expression of stress marker candidates in the brain.
    [Show full text]
  • Potent Inhibition of Monoamine Oxidase B by a Piloquinone from Marine-Derived Streptomyces Sp. CNQ-027
    J. Microbiol. Biotechnol. (2017), 27(4), 785–790 https://doi.org/10.4014/jmb.1612.12025 Research Article Review jmb Potent Inhibition of Monoamine Oxidase B by a Piloquinone from Marine-Derived Streptomyces sp. CNQ-027 Hyun Woo Lee1, Hansol Choi2, Sang-Jip Nam2, William Fenical3, and Hoon Kim1* 1Department of Pharmacy and Research Institute of Life Pharmaceutical Sciences, Sunchon National University, Suncheon 57922, Republic of Korea 2Department of Chemistry and Nano Science, Ewha Womans University, Seoul 03760, Republic of Korea 3Center for Marine Biotechnology and Biomedicine, Scripps Institution of Oceanography, University of California, San Diego, La Jolla, CA 92093-0204, USA Received: December 19, 2016 Revised: December 27, 2016 Two piloquinone derivatives isolated from Streptomyces sp. CNQ-027 were tested for the Accepted: January 4, 2017 inhibitory activities of two isoforms of monoamine oxidase (MAO), which catalyzes monoamine neurotransmitters. The piloquinone 4,7-dihydroxy-3-methyl-2-(4-methyl-1- oxopentyl)-6H-dibenzo[b,d]pyran-6-one (1) was found to be a highly potent inhibitor of First published online human MAO-B, with an IC50 value of 1.21 µM; in addition, it was found to be highly effective January 9, 2017 against MAO-A, with an IC50 value of 6.47 µM. Compound 1 was selective, but not extremely *Corresponding author so, for MAO-B compared with MAO-A, with a selectivity index value of 5.35. Compound 1,8- Phone: +82-61-750-3751; dihydroxy-2-methyl-3-(4-methyl-1-oxopentyl)-9,10-phenanthrenedione (2) was moderately Fax: +82-61-750-3708; effective for the inhibition of MAO-B (IC = 14.50 µM) but not for MAO-A (IC > 80 µM).
    [Show full text]
  • Identification and Analysis of Hepatitis C Virus NS3 Helicase Inhibitors Using Nucleic Acid Binding Assays Sourav Mukherjee1, Alicia M
    Published online 27 June 2012 Nucleic Acids Research, 2012, Vol. 40, No. 17 8607–8621 doi:10.1093/nar/gks623 Identification and analysis of hepatitis C virus NS3 helicase inhibitors using nucleic acid binding assays Sourav Mukherjee1, Alicia M. Hanson1, William R. Shadrick1, Jean Ndjomou1, Noreena L. Sweeney1, John J. Hernandez1, Diana Bartczak1, Kelin Li2, Kevin J. Frankowski2, Julie A. Heck3, Leggy A. Arnold1, Frank J. Schoenen2 and David N. Frick1,* 1Department of Chemistry and Biochemistry, University of Wisconsin-Milwaukee, Milwaukee, WI 53211, 2University of Kansas Specialized Chemistry Center, University of Kansas, 2034 Becker Dr., Lawrence, KS 66047 and 3Department of Biochemistry and Molecular Biology, New York Medical College, Valhalla, NY 10595, USA Received March 26, 2012; Revised May 30, 2012; Accepted June 4, 2012 Downloaded from ABSTRACT INTRODUCTION Typical assays used to discover and analyze small All cells and viruses need helicases to read, replicate and molecules that inhibit the hepatitis C virus (HCV) repair their genomes. Cellular organisms encode NS3 helicase yield few hits and are often con- numerous specialized helicases that unwind DNA, RNA http://nar.oxfordjournals.org/ founded by compound interference. Oligonucleotide or displace nucleic acid binding proteins in reactions binding assays are examined here as an alternative. fuelled by ATP hydrolysis. Small molecules that inhibit After comparing fluorescence polarization (FP), helicases would therefore be valuable as molecular homogeneous time-resolved fluorescence (HTRFÕ; probes to understand the biological role of a particular Cisbio) and AlphaScreenÕ (Perkin Elmer) assays, helicase, or as antibiotic or antiviral drugs (1,2). For an FP-based assay was chosen to screen Sigma’s example, several compounds that inhibit a helicase Library of Pharmacologically Active Compounds encoded by herpes simplex virus (HSV) are potent drugs in animal models (3,4).
    [Show full text]
  • Evidence of Pyrimethamine and Cycloguanil Analogues As Dual Inhibitors of Trypanosoma Brucei Pteridine Reductase and Dihydrofolate Reductase
    pharmaceuticals Article Evidence of Pyrimethamine and Cycloguanil Analogues as Dual Inhibitors of Trypanosoma brucei Pteridine Reductase and Dihydrofolate Reductase Giusy Tassone 1,† , Giacomo Landi 1,†, Pasquale Linciano 2,† , Valeria Francesconi 3 , Michele Tonelli 3 , Lorenzo Tagliazucchi 2 , Maria Paola Costi 2 , Stefano Mangani 1 and Cecilia Pozzi 1,* 1 Department of Biotechnology, Chemistry and Pharmacy, Department of Excellence 2018–2022, University of Siena, via Aldo Moro 2, 53100 Siena, Italy; [email protected] (G.T.); [email protected] (G.L.); [email protected] (S.M.) 2 Department of Life Science, University of Modena and Reggio Emilia, via Campi 103, 41125 Modena, Italy; [email protected] (P.L.); [email protected] (L.T.); [email protected] (M.P.C.) 3 Department of Pharmacy, University of Genoa, Viale Benedetto XV n.3, 16132 Genoa, Italy; [email protected] (V.F.); [email protected] (M.T.) * Correspondence: [email protected]; Tel.: +39-0577-232132 † These authors contributed equally to this work. Abstract: Trypanosoma and Leishmania parasites are the etiological agents of various threatening Citation: Tassone, G.; Landi, G.; neglected tropical diseases (NTDs), including human African trypanosomiasis (HAT), Chagas disease, Linciano, P.; Francesconi, V.; Tonelli, and various types of leishmaniasis. Recently, meaningful progresses in the treatment of HAT, due to M.; Tagliazucchi, L.; Costi, M.P.; Trypanosoma brucei (Tb), have been achieved by the introduction of fexinidazole and the combination Mangani, S.; Pozzi, C. Evidence of therapy eflornithine–nifurtimox. Nevertheless, due to drug resistance issues and the exitance of Pyrimethamine and Cycloguanil animal reservoirs, the development of new NTD treatments is still required.
    [Show full text]