Drug Discovery for Leishmaniasis
For human health, leishmaniasis is among the most important protozoan diseases, superseded only by malaria. Globally, 10 to 12 million people are infected with 1.5 million new cases every year. The development of cheaper new drugs is urgently needed for this neglected disease that is developing resistance to current treatments. Chemotherapy remains the only treatment option for the bulk of patients. However, this is largely unaffordable for most. In the past three years numerous advances in drug discovery have been made for treating this disease by exploiting diverging metabolic pathways between the Leishmania enzymes and their hosts, using nanotechnology to target the immune cell phagolysosomes where Leishmania resides.
Drug Discovery for Leishmaniasis aims to provide a perspective of the current treatments and their challenges, blended with the emerging strategies and methodologies that will drive new target appraisals and drug developments, as well as addressing the molecular basis of resistance in Leishmania.
Recent studies have shown that leishmaniasis affects some of the poorest people in the world, with 95% of fatal cases occurring in only 6 countries. With the WHO goal of eliminating this public health problem in the South-east Asia Region by 2020, this book will be important for anyone who is interested in neglected tropical diseases.
Drug Discovery for Leishmaniasis, The Royal Society of Chemistry, 2017.
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Table of contents
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I. Appraisal of Leishmaniasis Chemotherapy, Current Status and Pipeline StrategiesChapter 1: Leishmaniasis, Impact and Therapeutic Needsp1-23ByByron AranaByron AranaSearch for other works by this author on:
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Chapter 2: Anti-leishmanial Drug Discovery: Past, Present and Future Perspectivesp24-36ByCharles E. MowbrayCharles E. MowbrayDrugs for Neglected Diseases initiative15 Chemin Louis Dunant1202 GenevaSwitzerland[email protected]Search for other works by this author on:
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Chapter 3: From Bench to Bedside: Development and Optimization of Clinical Therapies for Visceral Leishmaniasisp37-54ByThomas P. C. DorloThomas P. C. DorloDepartment of Pharmacy & Pharmacology, Antoni van Leeuwenhoek Hospital/The Netherlands Cancer InstituteAmsterdamThe NetherlandsSearch for other works by this author on:
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II. Methodologies and Medicinal Chemistry Strategies to Discover and Develop New TreatmentsChapter 4: Drug Assay Methodology in Leishmaniasis: From the Microplate to Image Analysisp55-76ByVanessa Yardley;Vanessa YardleyFaculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical MedicineKeppel StreetLondon WC1E 7HTUK[email protected]Search for other works by this author on:Markella KoniordouMarkella KoniordouFaculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical MedicineKeppel StreetLondon WC1E 7HTUK[email protected]Search for other works by this author on:
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Chapter 5: The Pursuit of Novel Anti-leishmanial Agents by High-throughput Screening (HTS) of Chemical Librariesp77-100ByImanol PeñaImanol PeñaSearch for other works by this author on:
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Chapter 6: Omics and Their Impact on the Development of Chemotherapy Against Leishmaniap101-129ByChristopher Fernández-Prada;Christopher Fernández-PradaUniversité de Montréal, Faculté de Médecine Vétérinaire – Département de Pathologie et Microbiologie3190 rue SicotteSaint-HyacintheJ2S 2M2Canada[email protected]Search for other works by this author on:Isabel M. Vincent;Isabel M. VincentUniversity of Glasgow, Institute of Infection, Immunity and InflammationGlasgowG12 8QQScotlandUKSearch for other works by this author on:Élodie Gazanion;Élodie GazanionUniversité de Montpellier – Maladies Infectieuses et Vecteurs: Ecologie, Génétique, Evolution et Contrôle -MiVEGEC (IRD224 – CNRS5290), Institut de Recherche pour le Développement (IRD)911 Avenue AgropolisMontpellierBP 64501FranceSearch for other works by this author on:Rubens L. Monte-NetoRubens L. Monte-NetoInstituto René RachouFundação Oswaldo Cruz, 1715, Av. Augusto de LimaBelo Horizonte30190-002BrazilSearch for other works by this author on:
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Chapter 7: In silico Tools for Target Identification and Drug Molecular Docking in Leishmaniap130-152ByNuria E. CampilloNuria E. CampilloSearch for other works by this author on:
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Chapter 8: Medicinal Chemistry Strategies to Discover New Leishmanicidal Drugsp153-178ByCarmen GilCarmen GilSearch for other works by this author on:
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Chapter 9: Natural Products as a Source of New Drugs Against Leishmaniap179-198ByJoão Henrique G. Lago;João Henrique G. LagoCentro de Ciências Naturais e Humanas, Universidade Federal do ABCSanto André, SP, 09210-180BrazilSearch for other works by this author on:Andre G. TemponeAndre G. TemponeCentre of Parasitology and Mycology, Instituto Adolfo LutzSão Paulo, SP, 01246-000Brazil[email protected]Search for other works by this author on:
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Chapter 10: Organometallic Compounds in Chemotherapy Against Leishmaniap199-223ByBruno Rodrigues do Prado;Bruno Rodrigues do PradoDepartment of Chemistry, Institute of Exact Sciences, Federal University of Minas Gerais (UFMG)Av. Antônio Carlos 6627, Belo Horizonte 31270-901Minas GeraisBrazilSearch for other works by this author on:Arshad Islam;Arshad IslamDepartment of Physiology and Biophysics, Institute of Biological Sciences, Federal University of Minas Gerais (UFMG)Av. Antônio Carlos 6627, Belo Horizonte 31270-901Minas GeraisBrazil[email protected]Department of Chemistry, Institute of Exact Sciences, Federal University of Minas Gerais (UFMG)Av. Antônio Carlos 6627, Belo Horizonte 31270-901Minas GeraisBrazilSearch for other works by this author on:Frédéric Frézard;Frédéric FrézardDepartment of Chemistry, Institute of Exact Sciences, Federal University of Minas Gerais (UFMG)Av. Antônio Carlos 6627, Belo Horizonte 31270-901Minas GeraisBrazilSearch for other works by this author on:Cynthia DemicheliCynthia DemicheliDepartment of Physiology and Biophysics, Institute of Biological Sciences, Federal University of Minas Gerais (UFMG)Av. Antônio Carlos 6627, Belo Horizonte 31270-901Minas GeraisBrazil[email protected]Search for other works by this author on:
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Chapter 11: New Avenues for Drug Delivery in Leishmania: Using Treatment of Visceral Leishmaniasis with Amphotericin B as an Exemplarp224-234ByKatharine C. Carter;Katharine C. CarterStrathclyde Institute for Pharmacy and Biomedical Sciences, University of Strathclyde161 Cathedral StreetGlasgow G4 0REScotlandUK[email protected]Search for other works by this author on:Alexander B. MullenAlexander B. MullenStrathclyde Institute for Pharmacy and Biomedical Sciences, University of Strathclyde161 Cathedral StreetGlasgow G4 0REScotlandUK[email protected]Search for other works by this author on:
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III. The Quest for Achille's Heel of Leishmania. Singular Targets as New Avenues for Drug DevelopmentChapter 12: Addressing the Molecular Biology of Leishmania for Drug Developmentp235-247ByBrianna Norris-Mullins;Brianna Norris-MullinsEck Institute for Global Health, Department of Biological Sciences, University of Notre DameNotre DameIN46556USA[email protected]Search for other works by this author on:Miguel A. MoralesMiguel A. MoralesEck Institute for Global Health, Department of Biological Sciences, University of Notre DameNotre DameIN46556USA[email protected]Search for other works by this author on:
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Chapter 13: The Physical Matrix of the Plasma Membrane as a Target: The Charm of Drugs with Low Specificityp248-281ByLuis Rivas;Luis RivasDepartment of Chemical and Physical Biology, Centro de Investigaciones Biológicas (CSIC)Ramiro de Maeztu 928040 MadridSpain[email protected]Search for other works by this author on:Montserrat Nácher-Vázquez;Montserrat Nácher-VázquezDepartment of Chemical and Physical Biology, Centro de Investigaciones Biológicas (CSIC)Ramiro de Maeztu 928040 MadridSpain[email protected]Search for other works by this author on:David AndreuDavid AndreuDepartment of Experimental and Health Sciences, Pompeu Fabra University, Barcelona Biomedical Research Park08003 BarcelonaSpainSearch for other works by this author on:
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Chapter 14: Nutrient Transport and Sensing as Pharmacological Targets for Leishmaniasisp282-296ByDan ZilbersteinDan ZilbersteinSearch for other works by this author on:
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Chapter 15: Carbon Metabolism as a Drug Target in Leishmaniap297-315ByHéctor Acosta;Héctor AcostaLaboratorio de Enzimología de Parásitos, Departamento de Biología, Facultad de Ciencias, Universidad de Los AndesMérida 5101VenezuelaSearch for other works by this author on:Meng Yuan;Meng YuanCentre for Translational and Chemical Biology, School of Biological Sciences, The University of EdinburghThe King's Buildings, Michael Swann Building, Max Born CrescentEdinburgh EH9 3BFScotlandUK[email protected]Search for other works by this author on:Ana J. Cáceres;Ana J. CáceresLaboratorio de Enzimología de Parásitos, Departamento de Biología, Facultad de Ciencias, Universidad de Los AndesMérida 5101VenezuelaSearch for other works by this author on:Wilfredo A. Quiñones;Wilfredo A. QuiñonesLaboratorio de Enzimología de Parásitos, Departamento de Biología, Facultad de Ciencias, Universidad de Los AndesMérida 5101VenezuelaSearch for other works by this author on:Juan Luis Concepción;Juan Luis ConcepciónLaboratorio de Enzimología de Parásitos, Departamento de Biología, Facultad de Ciencias, Universidad de Los AndesMérida 5101VenezuelaSearch for other works by this author on:Paul A. M. MichelsPaul A. M. MichelsCentre for Translational and Chemical Biology, School of Biological Sciences, The University of EdinburghThe King's Buildings, Michael Swann Building, Max Born CrescentEdinburgh EH9 3BFScotlandUK[email protected]Centre for Immunity, Infection and Evolution, School of Biological Sciences, The University of EdinburghThe King's Buildings, Ashworth Building, Charlotte Auerbach RoadEdinburgh EH9 3FLScotlandUKSearch for other works by this author on:
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Chapter 16: The Redox Metabolism and Oxidative Stress in Leishmania as a Crossroads for the Lethal Effect of Drugsp316-347ByHelena Castro;Helena Castroi3S—Instituto de Investigação e Inovação em Saúde, Universidade do PortoPortugal[email protected][email protected]IBMC—Instituto de Biologia Molecular e Celular, Universidade do PortoRua Alfredo Allen 2084200-135 PortoPortugalSearch for other works by this author on:Margarida Duarte;Margarida Duartei3S—Instituto de Investigação e Inovação em Saúde, Universidade do PortoPortugal[email protected][email protected]IBMC—Instituto de Biologia Molecular e Celular, Universidade do PortoRua Alfredo Allen 2084200-135 PortoPortugalSearch for other works by this author on:Ana M. TomásAna M. Tomási3S—Instituto de Investigação e Inovação em Saúde, Universidade do PortoPortugal[email protected][email protected]IBMC—Instituto de Biologia Molecular e Celular, Universidade do PortoRua Alfredo Allen 2084200-135 PortoPortugalICBAS—Instituto de Ciências Biomédicas Abel Salazar, Universidade do PortoRua de Jorge Viterbo Ferreira 2284050-313 PortoPortugalSearch for other works by this author on:
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Chapter 17: DNA Topoisomerases as Promising Targets for Leishmania Chemotherapyp348-370ByRosa M Reguera;Rosa M RegueraDepartamento de Ciencias Biomédicas, Facultad de Veterinaria, Universidad de León, Campus de Vegazana s/n24071 LeónSpain[email protected]Search for other works by this author on:José M. Escudero-Martínez;José M. Escudero-MartínezDepartamento de Ciencias Biomédicas, Facultad de Veterinaria, Universidad de León, Campus de Vegazana s/n24071 LeónSpain[email protected]Search for other works by this author on:Bárbara Domínguez-Asenjo;Bárbara Domínguez-AsenjoDepartamento de Ciencias Biomédicas, Facultad de Veterinaria, Universidad de León, Campus de Vegazana s/n24071 LeónSpain[email protected]Search for other works by this author on:Camino Gutiérrez-Corbo;Camino Gutiérrez-CorboDepartamento de Ciencias Biomédicas, Facultad de Veterinaria, Universidad de León, Campus de Vegazana s/n24071 LeónSpain[email protected]Search for other works by this author on:Rafael Balaña-FouceRafael Balaña-FouceDepartamento de Ciencias Biomédicas, Facultad de Veterinaria, Universidad de León, Campus de Vegazana s/n24071 LeónSpain[email protected]Search for other works by this author on:
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Chapter 18: Molecular Basis of Drug Resistance in Leishmaniap371-386ByAnnelies Mondelaers;Annelies MondelaersLaboratory for Microbiology, Parasitology and Hygiene (LMPH), University of AntwerpUniversiteitsplein 1B-2610 Wilrijk (Antwerp)Belgium[email protected][email protected]Search for other works by this author on:Sarah Hendrickx;Sarah HendrickxLaboratory for Microbiology, Parasitology and Hygiene (LMPH), University of AntwerpUniversiteitsplein 1B-2610 Wilrijk (Antwerp)Belgium[email protected][email protected]Search for other works by this author on:Guy Caljon;Guy CaljonLaboratory for Microbiology, Parasitology and Hygiene (LMPH), University of AntwerpUniversiteitsplein 1B-2610 Wilrijk (Antwerp)Belgium[email protected][email protected]Search for other works by this author on:Louis MaesLouis MaesLaboratory for Microbiology, Parasitology and Hygiene (LMPH), University of AntwerpUniversiteitsplein 1B-2610 Wilrijk (Antwerp)Belgium[email protected][email protected]Search for other works by this author on:
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Chapter 19: The Macrophage–Parasite Interface as a Chemotherapeutic Target in Leishmaniasisp387-395ByAlbert DescoteauxAlbert DescoteauxSearch for other works by this author on:
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