☆ 4.5 Review

Are patents important indicators of innovation for Chagas disease treatment?

EXPERT OPINION ON THERAPEUTIC PATENTS (2023)

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Article Parasitology

On-site experience of a project to increase access to diagnosis and treatment of Chagas disease in high-risk endemic areas of Colombia

Rafael Herazo et al.

Summary: Colombia has a large burden of Chagas disease, but only a small percentage of the population has access to diagnosis and treatment. A patient-centered roadmap initiated in 2015 in five endemic municipalities has shown success in increasing testing numbers and reducing time between diagnosis and treatment.

ACTA TROPICA (2022)

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Review Microbiology

Protozoan phagotrophy from predators to parasites: An overview of the enigmatic cytostome-cytopharynx complex of Trypanosoma cruzi

Ronald Drew Etheridge

Summary: Feeding is a fundamental behavior for living organisms, and various strategies have evolved to capture energy and nutrients. Heterotrophic protozoans use self-generated currents to guide prey into an ancient oral apparatus, called the cytostome-cytopharynx complex. One class of these predators gave rise to a lineage of parasitic protozoa, the trypanosomatids, which can infect a wide range of organisms. The parasitic species Trypanosoma cruzi retains this ancestral organelle and uses it as its primary mode of endocytosis. This review highlights foundational observations and pressing questions about the mechanistic basis of the cytostome-cytopharynx complex. It proposes T. cruzi as an excellent model system to study protozoal phagotrophy and enhance our understanding of fundamental eukaryotic biology.

JOURNAL OF EUKARYOTIC MICROBIOLOGY (2022)

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Article Chemistry, Multidisciplinary

Identification of Leucinostatins from Ophiocordyceps sp. as Antiparasitic Agents against Trypanosoma cruzi

Jean A. Bernatchez et al.

Summary: The study identified five leucinostatins (A, B, F, NPDG C, and NPDG D) as potent inhibitors of the intracellular amastigote form of T. cruzi, and leucinostatin B also demonstrated in vivo suppression of T. cruzi in a mouse model of Chagas disease. These findings suggest a potential cross-trypanocidal compound class and provide a platform for further chemical derivatization for the development of effective treatments against T. cruzi.

ACS OMEGA (2022)

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Article Pharmacology & Pharmacy

Clinical and echocardiographic characteristics after six months of sacubitril/valsartan in Chagas heart disease - A case series

Clara Salles Figueiredo et al.

Summary: A study in Brazil evaluated a case series of Chagas heart disease patients using sacubitril/valsartan, finding symptomatic improvement after 6 months but no changes in ventricular remodelling, with high mortality and hospitalization rates. These results highlight the importance of studying the effectiveness of sacubitril/valsartan in Chagas heart disease to better understand its impact on these individuals.

BRITISH JOURNAL OF CLINICAL PHARMACOLOGY (2022)

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Review Chemistry, Medicinal

Why do few drug delivery systems to combat neglected tropical diseases reach the market? An analysis from the technology's stages

Jabson Herber Profiro de Oliveira et al.

Summary: Many drugs used to combat Schistosomiasis, Chagas disease, and Leishmaniasis have clinical limitations, but drug delivery systems (DDSs) are seen as a viable option to overcome these limitations. Analyzing the level of development of DDS patents can help determine the necessary steps for technologies to reach the market. Lack of integration between academia and industry for funding and continued research is identified as a barrier for the development of DDSs for neglected tropical diseases.

EXPERT OPINION ON THERAPEUTIC PATENTS (2022)

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Review Microbiology

Worldwide Control and Management of Chagas Disease in a New Era of Globalization: a Close Look at Congenital Trypanosoma cruzi Infection

Alba Abras et al.

Summary: Population movements have made Chagas disease a global public health issue. Despite efforts to control transmission in Latin American countries where the disease is endemic, congenital Chagas disease remains a significant challenge.

CLINICAL MICROBIOLOGY REVIEWS (2022)

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Article Public, Environmental & Occupational Health

Estimating chagas disease prevalence and number of underdiagnosed, and undertreated individuals in Spain

Miriam Navarro et al.

Summary: This study estimated the prevalence of Chagas disease and the number of undetected and untreated individuals in Spain. The burden of the disease is considerable, with high rates of underdiagnosis and undertreatment, particularly in women of childbearing age. However, there has been improvement in children since the implementation of antenatal screening programs.

TRAVEL MEDICINE AND INFECTIOUS DISEASE (2022)

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Review Medicine, General & Internal

Accuracy of Diagnostic Tests for the Detection of Chagas Disease: A Systematic Review and Meta-Analysis

Mayron Antonio Candia-Puma et al.

Summary: This systematic review and meta-analysis examined the accuracy of diagnostic tests for Chagas disease over a thirty-year period. The results showed that ELISA and qPCR techniques had higher accuracy in diagnosing chronic and acute phases of the disease, respectively. Future studies should focus on developing new diagnostic approaches for Chagas disease.

DIAGNOSTICS (2022)

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Article Immunology

The repositioned drugs disulfiram/diethyldithiocarbamate combined to benznidazole: Searching for Chagas disease selective therapy, preventing toxicity and drug resistance

Juliana Almeida-Silva et al.

Summary: This study tested the combination therapy of benznidazole (BZ) and the repositioned drug disulfiram (DSF) and its derivative diethyldithiocarbamate (DETC) on Trypanosoma cruzi. The results showed that the DETC-BZ combination had a synergistic effect in reducing parasite proliferation and decreasing toxicity. The combination therapy also showed efficacy against drug-resistant strains of Trypanosoma cruzi.

FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY (2022)

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Article Pharmacology & Pharmacy

Pharmaceutical agents for the treatment of Chagas disease: patenting trends in the 2016-2021 period

Viridiana Flores-Quiroz et al.

Summary: The treatment of American trypanosomiasis, specifically Chagas disease, receives little attention in the field of patents, with minimal upward trend.

PHARMACEUTICAL PATENT ANALYST (2022)

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Article Anthropology

Chagas Disease across Contexts: Scientific Knowledge in a Globalized World

Luciano G. Levin et al.

Summary: Chagas disease, as the most important endemic disease in Latin America, has been progressively recognized as a significant public issue. Research has primarily focused on the biological characterization of the parasite, with different countries' research strategies being influenced by endemicity and research traditions. This analysis helps in better understanding the construction of Chagas disease as a social and scientific problem.

MEDICAL ANTHROPOLOGY (2021)

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Article Medicine, Research & Experimental

Advances in the treatment of Chagas disease: Promising new drugs, plants and targets

Paola Garcia-Huertas et al.

Summary: Chagas disease is currently treated with only two drugs, benznidazole and nifurtimox, which have limitations including efficacy in specific infection stages, adverse effects, and parasite resistance. Some institutions and research groups are exploring new therapeutic alternatives through strategies like dosage modification, drug repurposing, combined therapy, the study of medicinal plants, and identification of essential parasite genes for targeted drug design. Collaboration and knowledge exchange among these entities could lead to the development of innovative treatments for Chagas disease.

BIOMEDICINE & PHARMACOTHERAPY (2021)

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Editorial Material Pharmacology & Pharmacy

Are academia-pharma partnerships essential for novel drug discovery in the time of the COVID-19 pandemic?

Joel Lexchin

EXPERT OPINION ON DRUG DISCOVERY (2021)

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Review Chemistry, Multidisciplinary

Ubiquitination and the Proteasome as Drug Targets in Trypanosomatid Diseases

Marie-Jose Bijlmakers

Summary: Eukaryotic pathogens such as Trypanosoma brucei, Trypanosoma cruzi, and Leishmania cause debilitating diseases with limited treatment options. Targeting the ubiquitin-proteasome system in these parasites shows potential for discovering therapeutic drugs with better efficacy and safety. Recent progress in developing trypanosomatid-selective proteasome inhibitors and targeting key enzymes in ubiquitination suggests promising strategies for treating these diseases.

FRONTIERS IN CHEMISTRY (2021)

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Article Public, Environmental & Occupational Health

Product patents and access to innovative medicines

Rong Dai et al.

Summary: The Agreement on Trade-Related Aspects of Intellectual Property Rights (TRIPS) has significant impacts on global access to medicines by making it obligatory for member states to protect pharmaceutical product patents. Introducing product patents can speed up the launch of innovative medicines, but there is little evidence that this improves drug availability in low-income countries. Disease-specific global policy responses have led to more affordable prices for HIV/AIDS, malaria, and tuberculosis medicines, while brand competition in the market can effectively drive down prices of both originator and generic medicines. Multiple generic entry is crucial to achieving drug affordability.

SOCIAL SCIENCE & MEDICINE (2021)

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Review Infectious Diseases

Roadblocks in Chagas disease care in endemic and nonendemic countries: Argentina, Colombia, Spain, and the United States. The NET-Heart project

Andres F. Miranda-Arboleda et al.

Summary: The author highlights the global impact of Chagas disease in Latin America, emphasizing the importance of improving access to care for CD patients. They identify barriers to early diagnosis and treatment, cultural beliefs, and stigma as key challenges in addressing the disease burden worldwide. By identifying and addressing these barriers nationally and globally, appropriate policies and public health programs can be developed to reduce the impact of Chagas disease.

PLOS NEGLECTED TROPICAL DISEASES (2021)

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Review Microbiology

Microbial proteasomes as drug targets

Hao Zhang et al.

Summary: Proteasomes are ATP-dependent, N-terminal nucleophile hydrolases that are essential for intracellular protein turnover and present in all biological kingdoms. Inhibiting proteasomes can be harmful to cell viability, but proteasome inhibitor drugs have revolutionized the treatment of multiple myeloma. Efforts are being made to develop inhibitors selective for microbial proteasomes, with promising progress in targeting pathogenic microbes for diseases like leishmaniasis and Chagas disease.

PLOS PATHOGENS (2021)

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Article Chemistry, Medicinal

Scaffold-Hopping Strategy on a Series of Proteasome Inhibitors Led to a Preclinical Candidate for the Treatment of Visceral Leishmaniasis

Michael Thomas et al.

Summary: An urgent need for new treatments for visceral leishmaniasis prompted the discovery of a preclinical candidate, GSK3494245/DDD01305143, through a medicinal chemistry program. The compound, identified through extensive scaffold-hopping exercise, showed in vivo efficacy as a proteasome inhibitor, shedding light on structure-activity relationships in the series.

JOURNAL OF MEDICINAL CHEMISTRY (2021)

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Article Infectious Diseases

New regimens of benznidazole monotherapy and in combination with fosravuconazole for treatment of Chagas disease (BENDITA): a phase 2, double-blind, randomised trial

Faustino Torrico et al.

Summary: The study evaluated the efficacy and safety of new benznidazole monotherapy regimens and combinations with fosravuconazole in the treatment of Chagas disease. Results showed that benznidazole induced effective antiparasitic response and was well tolerated in adult patients with chronic Chagas disease.

LANCET INFECTIOUS DISEASES (2021)

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Review Biochemistry & Molecular Biology

An Overview on Target-Based Drug Design against Kinetoplastid Protozoan Infections: Human African Trypanosomiasis, Chagas Disease and Leishmaniases

Violeta Kourbeli et al.

Summary: Protozoan diseases such as HAT, CD, and leishmaniases are a universal concern with current treatment regimens being insufficient. Target-based design offers new potential drug candidates for these neglected diseases.

MOLECULES (2021)

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Article Parasitology

Phenylbenzothiazole derivatives: effects against a Trypanosoma cruzi infection and toxicological profiles

Sarai Martinez-Ceron et al.

Summary: The study found that BZT4 was more selective and effective than the reference drug during the infective stage of Chagas disease. In a short-term in vivo model, BZT4 initially reduced parasitemia by 40%, but levels later returned to baseline. Long-term assessment showed only a 30% reduction in parasitemia by day 20 with a dose of 16mg/kg. The compound did not cause liver damage in a 21-day toxicity test, but altered protein concentrations and profiles in neuronal cells, potentially affecting the central nervous system. Further research is needed to improve the in vivo trypanocidal activity of BZT4 based on the better in vitro effect.

PARASITOLOGY RESEARCH (2021)

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Review Infectious Diseases

A systematic review of historical and current trends in Chagas disease

Diego-Abelardo Alvarez-Hernandez et al.

Summary: The systematic review analyzed Chagas disease case reports, revealing that most patients were from endemic countries and presented with symptoms such as fever, dyspnea, and constipation. Many patients were diagnosed in the chronic stage, with a lower rate of treatment administration.

THERAPEUTIC ADVANCES IN INFECTIOUS DISEASE (2021)

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Article Infectious Diseases

Poverty, Migration, and Chagas Disease

Felipe Guhl et al.

Summary: Chagas disease is a serious public health problem in Latin America, associated with poverty and poor housing conditions. Despite efforts by governments and the WHO/PAHO to control the disease, various factors such as human migration, deforestation, and climate change contribute to its continued transmission.

CURRENT TROPICAL MEDICINE REPORTS (2021)

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Review Microbiology

Chagas Disease in the United States: a Public Health Approach

Caryn Bern et al.

CLINICAL MICROBIOLOGY REVIEWS (2020)

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Review Pharmacology & Pharmacy

Why hasn't there been more progress in new Chagas disease drug discovery?

Alane Beatriz Vermelho et al.

EXPERT OPINION ON DRUG DISCOVERY (2020)

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Editorial Material Pharmacology & Pharmacy

Challenges and opportunities with drug repurposing: finding strategies to find alternative uses of therapeutics

Alan Talevi et al.

EXPERT OPINION ON DRUG DISCOVERY (2020)

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Article Medicine, General & Internal

Chagas disease: still a neglected emergency?

Renato D Lopes et al.

LANCET (2020)

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Review Chemistry, Medicinal

The role of imidazole and benzimidazole heterocycles in Chagas disease: A review

Ivan Beltran-Hortelano et al.

EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY (2020)

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Review Pharmacology & Pharmacy

Emerging agents for the treatment of Chagas disease: what is in the preclinical and clinical development pipeline?

Nieves Martinez-Peinado et al.

EXPERT OPINION ON INVESTIGATIONAL DRUGS (2020)

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Review Biochemistry & Molecular Biology

Chagas Disease: Perspectives on the Past and Present and Challenges in Drug Discovery

Felipe Raposo Passos Mansoldo et al.

MOLECULES (2020)

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Article Biochemistry & Molecular Biology

Synthesis and biological evaluation of new long-chain squaramides as anti-chagasic agents in the BALB/c mouse model

Ruben Martin-Escolano et al.

BIOORGANIC & MEDICINAL CHEMISTRY (2019)

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Article Multidisciplinary Sciences

Preclinical candidate for the treatment of visceral leishmaniasis that acts through proteasome inhibition

Susan Wyllie et al.

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (2019)

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Article Cell Biology

Quantitative phosphoproteome and proteome analyses emphasize the influence of phosphorylation events during the nutritional stress of Trypanosoma cruzi: the initial moments of in vitro metacyclogenesis

Aline Castro Rodrigues Lucena et al.

CELL STRESS & CHAPERONES (2019)

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Review Public, Environmental & Occupational Health

Chagas Disease: From Discovery to a Worldwide Health Problem

Karita Claudia Freitas Lidani et al.

FRONTIERS IN PUBLIC HEALTH (2019)

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Article Biochemistry & Molecular Biology

Facile Synthesis of a Series of Non-Symmetric Thioethers Including a Benzothiazole Moiety and Their Use as Efficient In Vitro anti-Trypanosoma cruzi Agents

Alcives Avila-Sorrosa et al.

MOLECULES (2019)

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Review Pharmacology & Pharmacy

Artificial Intelligence for Clinical Trial Design

Stefan Harrer et al.

TRENDS IN PHARMACOLOGICAL SCIENCES (2019)

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Article Public, Environmental & Occupational Health

Congenital Transmission of Trypanosoma cruzi in Argentina, Honduras, and Mexico: An Observational Prospective Study

Pierre Buekens et al.

AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE (2018)

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Article Microbiology

Benefits of Ascorbic Acid in Association with Low-Dose Benznidazole in Treatment of Chagas Disease

Maiara Voltarelli Providello et al.

ANTIMICROBIAL AGENTS AND CHEMOTHERAPY (2018)

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Editorial Material Infectious Diseases

The long road towards a safe and effective treatment of chronic Chagas disease

Julio A. Urbina

LANCET INFECTIOUS DISEASES (2018)

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Letter Cardiac & Cardiovascular Systems

Post hoc analyses of SHIFT and PARADIGM-HF highlight the importance of chronic Chagas' cardiomyopathy Comment on: Safety profile and efficacy of ivabradine in heart failure due to Chagas heart disease: a post hoc analysis of the SHIFT trial by Bocchi et al.

Felix J. A. Ramires et al.

ESC HEART FAILURE (2018)

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Article Cardiac & Cardiovascular Systems

Benznidazole and Posaconazole in Eliminating Parasites in Asymptomatic T. Cruzi Carriers The STOP-CHAGAS Trial

Carlos A. Morillo et al.

JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY (2017)

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Article Biochemistry & Molecular Biology

Repositioning FDA Drugs as Potential Cruzain Inhibitors from Trypanosoma cruzi: Virtual Screening, In Vitro and In Vivo Studies

Isidro Palos et al.

MOLECULES (2017)

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Article Public, Environmental & Occupational Health

Patent landscape of neglected tropical diseases: an analysis of worldwide patent families

Folahanmi Tomiwa Akinsolu et al.

GLOBALIZATION AND HEALTH (2017)

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Article Multidisciplinary Sciences

Quantitative proteome and phosphoproteome analyses highlight the adherent population during Trypanosoma cruzi metacyclogenesis

Juliana C. Amorim et al.

SCIENTIFIC REPORTS (2017)

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Article Biochemistry & Molecular Biology

Synthesis and biological evaluation of potential inhibitors of the cysteine proteases cruzain and rhodesain designed by molecular simplification

Saulo Fehelberg Pinto Braga et al.

BIOORGANIC & MEDICINAL CHEMISTRY (2017)

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Review Chemistry, Medicinal

Detection and treatment of Trypanosoma cruzi: a patent review (2011-2015)

Juan B. Rodriguez et al.

EXPERT OPINION ON THERAPEUTIC PATENTS (2016)

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Article Multidisciplinary Sciences

Proteasome inhibition for treatment of leishmaniasis, Chagas disease and sleeping sickness

Shilpi Khare et al.

NATURE (2016)

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Review Infectious Diseases

The use of posaconazole against Chagas disease

Israel Molina et al.

CURRENT OPINION IN INFECTIOUS DISEASES (2015)

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Article Multidisciplinary Sciences

New Compound Sets Identified from High Throughput Phenotypic Screening Against Three Kinetoplastid Parasites: An Open Resource

Imanol Pena et al.

SCIENTIFIC REPORTS (2015)

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Article Microbiology

Antitrypanosomal Activity of Fexinidazole Metabolites, Potential New Drug Candidates for Chagas Disease

Maria T. Bahia et al.

ANTIMICROBIAL AGENTS AND CHEMOTHERAPY (2014)

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Review Cardiac & Cardiovascular Systems

Epidemiology of Chagas disease in Europe: many calculations, little knowledge

Joern Strasen et al.

CLINICAL RESEARCH IN CARDIOLOGY (2014)

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Article Chemistry, Medicinal

Synthesis and Biological Evaluation of N,N′-Squaramides with High in Vivo Efficacy and Low Toxicity: Toward a Low-Cost Drug against Chagas Disease

Francisco Olmo et al.

JOURNAL OF MEDICINAL CHEMISTRY (2014)

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Review Chemistry, Multidisciplinary

Anti-Trypanosoma cruzi Compounds: Our Contribution for the Evaluation and Insights on the Mode of Action of Naphthoquinones and Derivatives

Eufranio N. da Silva Junior et al.

JOURNAL OF THE BRAZILIAN CHEMICAL SOCIETY (2014)

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Review Parasitology

Ecoepidemiology, short history and control of Chagas disease in the endemic countries and the new challenge for non-endemic countries

Jose Rodrigues Coura et al.

MEMORIAS DO INSTITUTO OSWALDO CRUZ (2014)

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Article Medicine, General & Internal

Randomized Trial of Posaconazole and Benznidazole for Chronic Chagas' Disease

Israel Molina et al.

NEW ENGLAND JOURNAL OF MEDICINE (2014)

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Article Medicine, General & Internal

Angiotensin-Neprilysin Inhibition versus Enalapril in Heart Failure

John J. V. McMurray et al.

NEW ENGLAND JOURNAL OF MEDICINE (2014)

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Article Public, Environmental & Occupational Health

The drug and vaccine landscape for neglected diseases (2000-11): a systematic assessment

Belen Pedrique et al.

LANCET GLOBAL HEALTH (2013)

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Article Chemistry, Medicinal

Cyclosquaramides as Kinase Inhibitors with Anticancer Activity

Priam Villalonga et al.

CHEMMEDCHEM (2012)

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Article Chemistry, Medicinal

On the search for potential anti-Trypanosoma cruzi drugs: Synthesis and biological evaluation of 2-hydroxy-3-methylamino and 1,2,3-triazolic naphthoquinoidal compounds obtained by click chemistry reactions

Eufranio N. da Silva Junior et al.

EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY (2012)

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Article Immunology

Benznidazole-Resistance in Trypanosoma cruzi Is a Readily Acquired Trait That Can Arise Independently in a Single Population

Ana Maria Mejia et al.

JOURNAL OF INFECTIOUS DISEASES (2012)

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Article Biochemistry & Molecular Biology

Squaric acid: a valuable scaffold for developing antimalarials?

S. Praveen Kumar et al.

MEDCHEMCOMM (2012)

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Article Infectious Diseases

Fexinidazole: A Potential New Drug Candidate for Chagas Disease

Maria Terezinha Bahia et al.

PLOS NEGLECTED TROPICAL DISEASES (2012)

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Article Biochemistry & Molecular Biology

Novel 1,3,4-thiadiazolium-2-phenylamine chlorides derived from natural piperine as trypanocidal agents: Chemical and biological studies

Welisson da Silva Ferreira et al.

BIOORGANIC & MEDICINAL CHEMISTRY (2008)

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