Identification and Characterization of Novel Anti-Leishmanial Compounds
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Review Article Use of Antimony in the Treatment of Leishmaniasis: Current Status and Future Directions
SAGE-Hindawi Access to Research Molecular Biology International Volume 2011, Article ID 571242, 23 pages doi:10.4061/2011/571242 Review Article Use of Antimony in the Treatment of Leishmaniasis: Current Status and Future Directions Arun Kumar Haldar,1 Pradip Sen,2 and Syamal Roy1 1 Division of Infectious Diseases and Immunology, Indian Institute of Chemical Biology, Council of Scientific and Industrial Research, 4 Raja S. C. Mullick Road, Kolkata West Bengal 700032, India 2 Division of Cell Biology and Immunology, Institute of Microbial Technology, Council of Scientific and Industrial Research, Chandigarh 160036, India Correspondence should be addressed to Syamal Roy, [email protected] Received 18 January 2011; Accepted 5 March 2011 Academic Editor: Hemanta K. Majumder Copyright © 2011 Arun Kumar Haldar 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. In the recent past the standard treatment of kala-azar involved the use of pentavalent antimonials Sb(V). Because of progressive rise in treatment failure to Sb(V) was limited its use in the treatment program in the Indian subcontinent. Until now the mechanism of action of Sb(V) is not very clear. Recent studies indicated that both parasite and hosts contribute to the antimony efflux mechanism. Interestingly, antimonials show strong immunostimulatory abilities as evident from the upregulation of transplantation antigens and enhanced T cell stimulating ability of normal antigen presenting cells when treated with Sb(V) in vitro. Recently, it has been shown that some of the peroxovanadium compounds have Sb(V)-resistance modifying ability in experimental infection with Sb(V) resistant Leishmania donovani isolates in murine model. -
T. Cruzi Invasion Summary Leishmania Phagosome
What is happening in invasion? T. cruzi invasion- non phagocytic Phagocytosis Active invasion Yeast Trypanosoma cruzi Actin filaments Lamp-1 T. cruzi invasion summary Leishmania phagosome Treatment for kinetoplastid diseases HAT Early (these drugs cannot cross the blood/brain barrier) Suramin (1916) highly charged compound Mode of action (?) - inhibits metabolic enzymes (NAD+) Pentamidine (some resistance) Mode of action (?) - likely multiple targets Differential uptake of drug - parasite conc. mM quantites Late Melarsoprol (lipophilic) (1947) Highly toxic arsenical - up to 10% treated die Mode of action (?) - possibly energy metabolism Eflornithine (drug has similar affinity to mammalian enzyme) suicide inhibitor of ornithine decarboxylase blocking polyamine biosynthesis Treatments for HAT 1985 2005 Early Stage First-line drugs Pentamidine Pentamidine Suramin Suramin Clinical trials - DB 289 (Phase III) Pre-clinical stage - - Late-stage/CNS First-line drugs Melarsoprol Melarsoprol Eflornithine Clinical trials - Nifurtimox + Eflornithine Pre-clinical stage - - Treatment for kinetoplastid diseases Chagas Acute Nifurtimox 60-90 days Mode of action (?) ROS - then DNA damage Benznidazole 30-120 days Mode of action - thought to inhibit nucleic acid synthesis (ROS?) Chronic Virtually untreatable - just treat symptoms Treatments for Chagas 1985 2005 Acute Stage First-line drugs Benznidazole Benznidazole Nifurtimox Nifurtimox Clinical trials Allopurinal Indeterminate Stage Clinical trials - Benznidazole Chronic Stage First-line drugs - -
Topical Treatment of Cutaneous Leishmaniasis
Topical Treatment of Cutaneous Leishmaniasis Joseph EI-On, Ph.D., Rita Livshin, M.D., Zvi Even-Paz, M.D. , David Hamburger, Ph.D., and Louis Weinrauch, M. D . Department of Microbio logy and Immunology, Facult y of Hea lth Sciences, Dcn G urion University of the N cgev UE-O), Deer Sheva; Departmcnt of Dcrmatology, Hadassah Universi ty H ospital, Hebrcw University Had assa h Mcdical School (R L, ZE-P, LW), j erusalem; Teva Pharm aceutica l In dustries Ltd. (01-1 ), j erusa lem, Israel Six ty- seven patients, 19 fem :ll es and 48 m ales, 4-66 years develo pments did not affect the clinical he:ding process o ld , sufferin g fro m lesions o f cutaneous leishmaniasis which was generall y completed in a period of 10-30 d ays were treated to pica ll y with an o intme nt comprising 15% after termination of trea tment. In addition, 94% of the paro m o mycin sulfate and 12% m eth ylbenzethonium chl o treated lesio n s healed with little o r no scarring. N o adverse ride in white soft pa raffin (P-ointment, U .K . patent clinica l or laboratory side effe cts w ere observed except fo r GBll7237A). After 10 d ays of treatment, twice daily, the a burning sensation at the site of trea tment. Parasites iso_ lesio ns in 72% of the treated pati ents were free of parasites, lated fro m patients w ho failed to respond to topical treat_ 15% becam e free with in an additional 20 d ays, witho ut m ent were found to be susceptible to PR-MBC I in both further trea tment, and 13% failed to respond. -
Ce Document Est Le Fruit D'un Long Travail Approuvé Par Le Jury De Soutenance Et Mis À Disposition De L'ensemble De La Communauté Universitaire Élargie
AVERTISSEMENT Ce document est le fruit d'un long travail approuvé par le jury de soutenance et mis à disposition de l'ensemble de la communauté universitaire élargie. Il est soumis à la propriété intellectuelle de l'auteur. Ceci implique une obligation de citation et de référencement lors de l’utilisation de ce document. D'autre part, toute contrefaçon, plagiat, reproduction illicite encourt une poursuite pénale. Contact : [email protected] LIENS Code de la Propriété Intellectuelle. articles L 122. 4 Code de la Propriété Intellectuelle. articles L 335.2- L 335.10 http://www.cfcopies.com/V2/leg/leg_droi.php http://www.culture.gouv.fr/culture/infos-pratiques/droits/protection.htm UNIVERSITE DE LORRAINE 2018 ___________________________________________________________________________ FACULTE DE PHARMACIE THESE Présentée et soutenue publiquement Le 27 JUIN 2018, sur un sujet dédié à : LA MALADIE DE CHAGAS : DIAGNOSTIC, CLINIQUE ET PERSPECTIVES D’UNE MALADIE NÉGLIGÉE Pour obtenir Le Diplôme d'Etat de Docteur en Pharmacie Par Sébastien KAUFFMANN Né le 07/09/1988 à NANCY Membres du Jury Président : COULON JOEL, Maître de Conférences, faculté de pharmacie à Nancy Juges : BANAS SANDRINE, Maître de Conférences, faculté de pharmacie de Nancy BELLANGER XAVIER, Maître de Conférences, faculté de pharmacie de Nancy DUVAL NICOLE, Pharmacienne officinale UNIVERSITÉ DE LORRAINE FACULTÉ DE PHARMACIE Année universitaire 2017-2018 DOYEN Francine PAULUS Vice-Doyen/Directrice des études Virginie PICHON Conseil de la Pédagogie Présidente, -
Manual for the Diagnosis and Treatment of Leishmaniasis
Republic of the Sudan Federal Ministry of Health Communicable and Non-Communicable Diseases Control Directorate MANUAL FOR THE DIAGNOSIS AND TREATMENT OF LEISHMANIASIS November 2017 Acknowledgements The Communicable and Non-Communicable Diseases Control Directorate (CNCDCD), Federal Ministry of Health, Sudan, would like to acknowledge all the efforts spent on studying, controlling and reducing morbidity and mortality of leishmaniasis in Sudan, which culminated in the formulation of this manual in April 2004, updated in October 2014 and again in November 2017. We would like to express our thanks to all National institutions, organizations, research groups and individuals for their support, and the international organization with special thanks to WHO, MSF and UK- DFID (KalaCORE). I Preface Leishmaniasis is a major health problem in Sudan. Visceral, cutaneous and mucosal forms of leishmaniasis are endemic in various parts of the country, with serious outbreaks occurring periodically. Sudanese scientists have published many papers on the epidemiology, clinical manifestations, diagnosis and management of these complex diseases. This has resulted in a better understanding of the pathogenesis of the various forms of leishmaniasis and has led to more accurate and specific diagnostic methods and better therapy. Unfortunately, many practitioners are unaware of these developments and still rely on outdated diagnostic procedures and therapy. This document is intended to help those engaged in the diagnosis, treatment and nutrition of patients with various forms of leishmaniasis. The guidelines are based on publications and experience of Sudanese researchers and are therefore evidence based. The guidelines were agreed upon by top researchers and clinicians in workshops organized by the Leishmaniasis Control response at the Communicable and Non-Communicable Diseases Control Directorate, Federal Ministry of Health, Sudan. -
University of Dundee Anti-Trypanosomatid Drug Discovery
University of Dundee Anti-trypanosomatid drug discovery Field, Mark C.; Horn, David; Fairlamb, Alan H.; Ferguson, Michael A. J.; Gray, David W.; Read, Kevin D. Published in: Nature Reviews Microbiology DOI: 10.1038/nrmicro.2016.193 Publication date: 2017 Document Version Peer reviewed version Link to publication in Discovery Research Portal Citation for published version (APA): Field, M. C., Horn, D., Fairlamb, A. H., Ferguson, M. A. J., Gray, D. W., Read, K. D., De Rycker, M., Torrie, L. S., Wyatt, P. G., Wyllie, S., & Gilbert, I. H. (2017). Anti-trypanosomatid drug discovery: an ongoing challenge and a continuing need. Nature Reviews Microbiology, 15(4), 217-231. https://doi.org/10.1038/nrmicro.2016.193 General rights Copyright and moral rights for the publications made accessible in Discovery Research 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 Discovery Research 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. Take down policy 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. Download date: 26. Sep. 2021 Vector-borne diseases series Antitrypanosomatid drug discovery: an ongoing challenge and a continuing need Mark C. -
Ehealth DSI [Ehdsi V2.2.2-OR] Ehealth DSI – Master Value Set
MTC eHealth DSI [eHDSI v2.2.2-OR] eHealth DSI – Master Value Set Catalogue Responsible : eHDSI Solution Provider PublishDate : Wed Nov 08 16:16:10 CET 2017 © eHealth DSI eHDSI Solution Provider v2.2.2-OR Wed Nov 08 16:16:10 CET 2017 Page 1 of 490 MTC Table of Contents epSOSActiveIngredient 4 epSOSAdministrativeGender 148 epSOSAdverseEventType 149 epSOSAllergenNoDrugs 150 epSOSBloodGroup 155 epSOSBloodPressure 156 epSOSCodeNoMedication 157 epSOSCodeProb 158 epSOSConfidentiality 159 epSOSCountry 160 epSOSDisplayLabel 167 epSOSDocumentCode 170 epSOSDoseForm 171 epSOSHealthcareProfessionalRoles 184 epSOSIllnessesandDisorders 186 epSOSLanguage 448 epSOSMedicalDevices 458 epSOSNullFavor 461 epSOSPackage 462 © eHealth DSI eHDSI Solution Provider v2.2.2-OR Wed Nov 08 16:16:10 CET 2017 Page 2 of 490 MTC epSOSPersonalRelationship 464 epSOSPregnancyInformation 466 epSOSProcedures 467 epSOSReactionAllergy 470 epSOSResolutionOutcome 472 epSOSRoleClass 473 epSOSRouteofAdministration 474 epSOSSections 477 epSOSSeverity 478 epSOSSocialHistory 479 epSOSStatusCode 480 epSOSSubstitutionCode 481 epSOSTelecomAddress 482 epSOSTimingEvent 483 epSOSUnits 484 epSOSUnknownInformation 487 epSOSVaccine 488 © eHealth DSI eHDSI Solution Provider v2.2.2-OR Wed Nov 08 16:16:10 CET 2017 Page 3 of 490 MTC epSOSActiveIngredient epSOSActiveIngredient Value Set ID 1.3.6.1.4.1.12559.11.10.1.3.1.42.24 TRANSLATIONS Code System ID Code System Version Concept Code Description (FSN) 2.16.840.1.113883.6.73 2017-01 A ALIMENTARY TRACT AND METABOLISM 2.16.840.1.113883.6.73 2017-01 -
Nationalinstitute of Genetics Japan
NATIONALINSTITUTE OF GENETICS JAPAN ANNUAL REPORT No. 23 1972 PublitJhMl 611 THE NATIONAL INSTITUTE OF GBNE'l1C8 IIiaimG. 8&uoktl-km, J.,.,. 1973 Annual Report of the National Institute of Genetics No. 23, 1972 I Published by The National Institute of Genetics, Japan 1973 CONTENTS General statement 1 Staff 2 Council.......... .. 5 Association for propagation of the knowledge of genetics .. 6 Projects of research for 1972 7 Researches carried out in 1972 .................................. 11 I. Molecular Genetics The 5'-terminal structure of cytoplasmic polyhedrosis virus (CPV) genome RNA. MIURA, K., SUGIURA, M. and WA- TANABE, K. 11 Terminal structure of single-stranded RNA transcribed by the cytoplasmic polyhedrosis (CP) virus. SHIMOTOHNO, K., FURUICHI, Y. and MIURA, K. 12 The 3'-terminal structure of Avian reovirus RNA. FURUICHI, Y. and MIURA, K. 13 Nucleotide ratio of the genome segments in a cytoplasmic polyh edrosis virus from silkworm. FURUICHI, Y., RAI, U. and .. MIURA, K. 13 II. Microbial Genetics Absence of messenger ribonucleic acid specific for flagellin in fla- mutants. SUZUKI, H. and IINO, T. 15 Ill. Biochemical Genetics Improved method for separation and identification of rat serum transferrins: Thin layer acrylamide-gel electrophoresis with acrinol pretreatment. MORIWAKI, K. .. .................. 17 The second scientific expedition to Southeast, Southwest and Central Asia for the study of rodents. IV. Electrophoretic survey of polymorphic transferrin types on the black rat, Rattus rattus. MORIWAKI, K., TSUCHIYA, K., KATO, H., YOSIDA, T. H. and SADAIE, T. 18 ii ANNUAL REPORT OF NATIONAL INSTITUTE OF GENETICS NO. 23 Serum transferrin polymorphism in the red-backed vole, Clethrio nomys rufocanus bedfordiae. -
Redalyc.Influence of Gentamicine on the Pharmacokinetic of A
Archivos Venezolanos de Farmacología y Terapéutica ISSN: 0798-0264 [email protected] Sociedad Venezolana de Farmacología Clínica y Terapéutica Venezuela Vásquez de Ricciardi, Laura; Scorza, José Vicente; Vicuña-Fernández, Nelson; Petit de Peña, Yaneira; Bendezú, Herminia; Vasquez, Libia; Yanez, Carlos Influence of gentamicine on the pharmacokinetic of a pentavalent antimonial compound Glucantime® Influence of gentamicine on Glucantime kinetic Archivos Venezolanos de Farmacología y Terapéutica, vol. 25, núm. 2, 2006, pp. 60-63 Sociedad Venezolana de Farmacología Clínica y Terapéutica Caracas, Venezuela Disponible en: http://www.redalyc.org/articulo.oa?id=55925204 Cómo citar el artículo Número completo Sistema de Información Científica Más información del artículo Red de Revistas Científicas de América Latina, el Caribe, España y Portugal Página de la revista en redalyc.org Proyecto académico sin fines de lucro, desarrollado bajo la iniciativa de acceso abierto Influence of gentamicine on the pharmacokinetic of a pentavalent antimonial compound Glucantime® Influence of gentamicine on Glucantime kinetic Laura Vásquez de Ricciardi 1, José Vicente Scorza 2, Nelson Vicuña-Fernández 3, Yaneira Petit de Peña 4, Herminia Bendezú 5, Libia Vasquez 6, Carlos Yanez 7 1 Doctora en Ciencias Médicas. Laboratorio de Farmacología., Facultad de Medicina Escuela de Medicina Valera. ULA. 2 Doctor en Parasitología. Centro de Investigaciones Parasitológicas ¨José W. Torrealba¨ NURR. ULA. 3 Médico Especialista en Farmacocinética. Laboratorio de Farmacología y Toxicología Facultad de Medicina ULA. Mérida, Venzuela. 4 Doctora en Química. Laboratorio de Espectroscopía Molecular. Facultad de Ciencias. La Hechicera. ULA. 5 Magister en Protozoología. Centro de Investigaciones Parasitológicas ¨José W. Torrealba¨ NURR, ULA. 6 Medico Microbiologo. Laboratorio de Microbiología. -
Adenosine-Proflavine Complex: a Self-Paired Parallel-Chain
Proc. Natl. Acad. Sci. USA Vol. 77, No. 4, pp. 1852-1856, April 1980 Biochemistry X-ray structure of a cytidylyl-3',5'-adenosine-proflavine complex: A self-paired parallel-chain double helical dimer with an intercalated acridine dye* (non-self-complementary pairing of adenine-adenine and protonated cytosine-cytosine/intercalation dynamics/ sugar-phosphate backbone stereochemistry/frameshift mutagenesis) E. WESTHOF AND M. SUNDARALINGAM Department of Biochemistry, College of Agricultural and Life Sciences, University of Wisconsin-Madison, Madison, Wisconsin 53706 Communicated by David R. Davies, December 31, 1979 ABSTRACT The non-self-complementary dinucleoside parallel-chain double helical dimer of cytidylyl-3',5'-adenosine monophosphate cytidylyl-3',5'-adenosine (CpA) forms a base- (CpA). The dinucleoside monophosphate CpA was chosen not paired parallel-chain dimer with an intercalated proflavine.The dimer complex possesses a right-handed helical twist. The dimer only because it constitutes the end portion of the invariant CCA helix has an irregular girth with a neutral adenine-adenine (A-A) terminus of all tRNAs, but also because it cannot form self- pair, hydrogen-bonded through the N6 and N7 sites (C1'... C1' complementary pairs. separation of 10.97 A), and a triply hydrogen-bonded protonated cytosine-cytosine (C-C) pair with a proton shared between the METHODS base N3 sites (C1'... C1' separation of 9.59 A). The torsion an- EXPERIMENTAL gles of the sugar-phosphate backbone are within their most Single crystals of a 1:1 complex of CpA and proflavine were preferred ranges and the sugar puckering sequence (5' - 3') is grown from an equimolar aqueous solution of proflavine he- C3'-endo, C2'-endo. -
Aads. See Aminoacetonitrile Derivatives
363 Index a anaerobic NADH-fumarate reductase AADs. See aminoacetonitrile derivatives system 275 (AADs) anthelmintic discovery ABZ-nitazoxanide 266 medicinal chemistry approaches ABZ-sulfone 260, 265, 266 CODP 242–245 ABZ-sulfoxide 260, 265, 266, 272 intervet multicyclics 235, 238 Acid fast bacilli (AFB) 329, 330 VAChT inhibitors 238, 240, 241 acoziborole 129, 130 new molecules, from patent literature acute fascioliasis 294 232–235 adult flukes 295, 300 anti-bacterial approach 169, 171 adult worms 164, 166, 170–172, 175, antibacterial therapy vs. host directed 180, 190–192, 194–198, 200, 201, therapy 354 206, 207, 254, 290, 293–296, 304 antibody-based therapeutics 67–69 African animal trypanosomiasis (AAT) anticancer drugs 194 118, 119 anti-microbial properties 271 albendazole 2, 3, 9, 169, 171, 227–229, metallo-organic ruthenium 257, 272, 275, 303 complexes 271 Alpha-1-acid glycoprotein (AGP) proteasome inhibitor 271, 273 203, 212 anti-foodborne trematode drugs 304, α-difluoromethylornithine 265 311 17-α-ethynylestradiol 298 anti-fungal agent 260 Alpinia nigra 307, 311 anti-fungal compound amphotericin B Alveolar echinococcosis (AE) 253 desoxycholate (cAMB) 267 benzimidazole treatments 257, anti-infective agents 259–261 anti-echinococcal activities 267 clinical presentation 255, 257 anti-malarial drugs 268 Aminoacetonitrile derivatives (AADs) extracellular protozoan parasites 233, 234, 238 267 patents 233 intracellular protozoan parasites amino-acetonitrile linker 234 267 amino-malononitrile linker 234 anti-infective thiazolide 260 amino ozonids 267 anti-malarial compounds 267 amino-pyrazole 147, 148 anti-malarial drugs 268 amphotericin B 2, 3, 7, 140, 143, 144, antimalarials dihydroartemisinin 267 148, 260, 267, 272, 275 anti-metacestodal activity 271 Neglected Tropical Diseases: Drug Discovery and Development, First Edition. -
The Proteasome As a Target: How Not Tidying up Can Have Toxic Consequences for Parasitic Protozoa Elizabeth A
COMMENTARY COMMENTARY The proteasome as a target: How not tidying up can have toxic consequences for parasitic protozoa Elizabeth A. Winzelera,1 and Sabine Ottiliea With modern drug discovery technologies, there are good pharmacokinetics, and is now being progressed opportunities to discover drugs that are uniquely toward human clinical trials. suited for treatment of specific parasitic diseases and In addition to its potential to radically improve the have few of the liabilities of older, historical medicines. treatment options for VL, another noteworthy feature In PNAS, Wyllie et al. (1) used state-of-the-art methods of the work is the elegant and thorough approach that to identify a clinical candidate for leishmaniasis and to was used to determine the mechanism of action of discover its mechanism of action. GSK3494245 in parasites. Suspecting that the mech- Leishmaniasis is a neglected parasitic infectious anism of action might be shared across closely related disease that can have different clinical manifestations parasites, Wyllie et al. (1) first tested a compound depending on the parasite species. Visceral leishman- from the series (compound 7) against a genome- iasis (VL) (also known as kala-azar or black fever), which wide Trypanosoma brucei RNA interference (RNAi) li- is caused by Leishmania donovani and Leishmania brary (5). This RNAi library consists of ∼750,000 clones, infantum, is the most severe form and marked by a each transformed with one RNAi construct under the swollen spleen. It is a significant cause of morbidity control of a tetracycline-inducible promoter and cov- in areas where the insect vector, the sandfly, is present ers >99% of the ∼7,500 nonredundant T.