4.5 Review

Emerging compounds and therapeutic strategies to treat infections from Trypanosoma brucei: an overhaul of the last 5-years patents

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Review Immunology

Pathogenicity and virulence of African trypanosomes: From laboratory models to clinically relevant hosts

Liam J. J. Morrison et al.

Summary: African trypanosomes are protozoa that are transmitted by vectors and cause significant disease in humans and animals. The severity of infection varies depending on the species of Trypanosoma and the host, making intervention design challenging. This review provides an overview of the current understanding of trypanosome determinants of infection progression and severity, highlighting knowledge gaps and opportunities for developing novel interventions.

VIRULENCE (2023)

Review Veterinary Sciences

An Update on African Trypanocide Pharmaceutics and Resistance

Keneth Iceland Kasozi et al.

Summary: African trypanosomiasis, both in animals and humans, is associated with different pathogens and drug resistance. Research is being conducted on new combination therapies.

FRONTIERS IN VETERINARY SCIENCE (2022)

Article Infectious Diseases

Human African trypanosomiasis cases diagnosed in non-endemic countries (2011-2020)

Jose R. Franco et al.

Summary: Sleeping sickness diagnosis in non-endemic countries is rare, but vigilance and surveillance should be maintained to contribute to the World Health Organization's elimination goals.

PLOS NEGLECTED TROPICAL DISEASES (2022)

Article Chemistry, Medicinal

Nitro compounds against trypanosomatidae parasites: Heroes or villains?

Paulo Fernando da Silva Santos-Junior et al.

Summary: This review presents a comprehensive overview of nitrocompounds that have been reported as inhibitors against Trypanosoma cruzi, T. brucei rhodesiense, and T. b. gambiense parasites. The activities and structure-activity relationship analyses of these compounds are highlighted, providing valuable information for research teams seeking novel trypa-nocidal and leishmanicidal agents.

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS (2022)

Review Pharmacology & Pharmacy

Anti-trypanosomatid structure-based drug design - lessons learned from targeting the folate pathway

Joanna Panecka-Hofman et al.

Summary: This article reviews the application of structure-based drug design approaches in discovering anti-Trypanosomatid compounds. Although some progress has been made, our incomplete understanding of parasite biology and biochemistry is currently hindering the discovery of selective anti-parasitic drugs.

EXPERT OPINION ON DRUG DISCOVERY (2022)

Article Public, Environmental & Occupational Health

Safety and efficacy of oral fexinidazole in children with gambiense human African trypanosomiasis: a multicentre, single-arm, open-label, phase 2-3 trial

Victor Kande Betu Kumesu et al.

Summary: The multicentre clinical trial of oral fexinidazole in pediatric patients with gambiense human African trypanosomiasis demonstrated that the drug is a safe and effective first-line treatment option across all disease stages.

LANCET GLOBAL HEALTH (2022)

Review Microbiology

Systematic Review and Meta-Analysis on Human African Trypanocide Resistance

Keneth Iceland Kasozi et al.

Summary: The resistance of Human African trypanosomiasis (HAT) is a challenge to its eradication. Resistance is associated with changes in pathogen receptors and the loss of certain genes. Clinical studies have shown high failure rates for certain therapies, indicating the presence of resistance.

PATHOGENS (2022)

Review Medicine, General & Internal

Recent progress in diagnosis and treatment of Human African Trypanosomiasis has made the elimination of this disease a realistic target by 2030

Andres Alvarez-Rodriguez et al.

Summary: Human African Trypanosomiasis (HAT) is a disease caused by parasites of the genus Trypanosoma brucei. Different subspecies cause different infections. Diagnosing and treating HAT has improved, but further research and improvements are needed.

FRONTIERS IN MEDICINE (2022)

Review Medicine, Research & Experimental

Fexinidazole for Human African Trypanosomiasis, the Fruit of a Successful Public-Private Partnership

Sonja Bernhard et al.

Summary: After a century of impractical and toxic chemotherapy, a new oral cure called Fexinidazole is now available for human African trypanosomiasis. It has been discovered and developed through extensive screening and testing in both cell cultures and animal models, and has shown promising results in clinical trials conducted in the Democratic Republic of the Congo. With its safety and effectiveness confirmed, Fexinidazole has been endorsed by the European Medicines Agency and included in the new treatment guidelines issued by the WHO.

DISEASES (2022)

Article Biochemistry & Molecular Biology

Immunoinformatic design of a putative multi-epitope vaccine candidate against Trypanosoma brucei gambiense

Ammar Usman Danazumi et al.

Summary: Human African trypanosomiasis (HAT) is a neglected tropical disease caused by flagellated parasites. It imposes a significant socio-economic burden on sub-Saharan African countries, and its control is hindered by drug ineffectiveness, complex dosing regimens, drug resistance, and lack of a vaccine. Researchers have utilized computational modeling and omics data to design a multi-epitope vaccine (MEV) composed of antigenic peptides, which offers improved antigenicity and safety. The designed MEV could serve as a potential candidate for targeting HAT.

COMPUTATIONAL AND STRUCTURAL BIOTECHNOLOGY JOURNAL (2022)

Review Biochemistry & Molecular Biology

Recent Advances in the Development of Broad-Spectrum Antiprotozoal Agents

Antonio Moreno-Herrera et al.

Summary: Parasitic infections caused by various protozoa affect millions of people worldwide annually, with limited pharmacological treatments. Developing new and more effective drugs could be crucial in improving therapy outcomes for parasitic diseases.

CURRENT MEDICINAL CHEMISTRY (2021)

Review Parasitology

Evolving Differentiation in African Trypanosomes

Juan F. Quintana et al.

Summary: Parasite differentiation is essential for adaptation to hosts and environments, with the transition between vertebrate and insect stages being well studied in African trypanosomes. Activation of advantageous metabolic pathways in the insect host leads to the formation of a 'stumpy' form. Various stimuli and stress conditions can trigger similar changes, suggesting a repurposing of a generic stress response for gains in parasite fitness during transmission.

TRENDS IN PARASITOLOGY (2021)

Article Parasitology

Naphthoquinone derivatives exhibit apoptosis-like effect and anti-trypanosomal activity against Trypanosoma evansi

Ruma Rani et al.

Summary: Six naphthoquinone derivatives were evaluated for their anti-trypanosomal activity against T. evansi, with NTQ1, NTQ3, and NTQ6 showing the most potential. These NTQs exhibited significant production of ROS and characteristics of apoptosis in an axenic culture of T. evansi.

VETERINARY PARASITOLOGY (2021)

Review Chemistry, Medicinal

Cruzain and Rhodesain Inhibitors: Last Decade of Advances in Seeking for New Compounds Against American and African Trypanosomiases

Igor Jose dos Santos Nascimento et al.

Summary: This review discusses the development of cruzain and rhodesain inhibitors in the past 10 years, which could serve as a basis for the discovery of new trypanocidal drugs in the future.118 studies on inhibitors of cruzain and rhodesain were identified, indicating the potential for developing new treatments against Chagas disease and sleeping sickness.

CURRENT TOPICS IN MEDICINAL CHEMISTRY (2021)

Review Pharmacology & Pharmacy

Naphthoquinones and Derivatives for Chemotherapy: Perspectives and Limitations of their Anti-trypanosomatids Activities

Luiza Dantas-Pereira et al.

Summary: Chagas disease, sleeping sickness, and leishmaniasis are neglected tropical diseases that particularly affect impoverished populations. Natural naphthoquinones and their derivatives show promising antiparasitic activity against trypanosomatids in vitro, suggesting their potential for development as alternative therapies.

CURRENT PHARMACEUTICAL DESIGN (2021)

Article Chemistry, Medicinal

Structure-Based Optimization of Quinazolines as Cruzain and TbrCATL Inhibitors

Elany Barbosa da Silva et al.

Summary: The study describes a competitive cruzain inhibitor and its analogs, which exhibit low micromolar inhibition of the target proteases, cidal activity against Trypanosoma cruzi, and potential therapeutic effects.

JOURNAL OF MEDICINAL CHEMISTRY (2021)

Article Biochemistry & Molecular Biology

Activity of Compounds from Temperate Propolis against Trypanosoma brucei and Leishmania mexicana

Adullah Alotaibi et al.

Summary: Ethanolic extracts of temperate zone propolis from the UK and Poland exhibited anti-trypanosomal activity, with compounds like naringenin 4 ',7-dimethyl ether and 4 '-methoxykaempferol showing the highest activity. Different compounds were isolated and characterized, showing varying levels of activity against drug-resistant strains of T. brucei and L. mexicana, without a clear structure-activity relationship observed. Multiple compounds from temperate propolis have anti-kinetoplastid activity.

MOLECULES (2021)

Article Microbiology

The Trypanosome UDP-Glucose Pyrophosphorylase Is Imported by Piggybacking into Glycosomes, Where Unconventional Sugar Nucleotide Synthesis Takes Place

Oriana Villafraz et al.

Summary: Trypanosomatids sequester glycolysis inside peroxisomes called glycosomes and have functional sugar nucleotide biosynthetic pathways in addition to cytosolic ones. The enzyme UDP-glucose pyrophosphorylase (UGP) is imported into glycosomes by piggybacking on phosphoenolpyruvate carboxykinase (PEPCK) without a known peroxisome-targeting signal, suggesting a unique mechanism for protein import. These findings shed light on the unconventional compartmentalization of metabolic pathways in trypanosomatids.
Review Microbiology

Regulation of Antigenic Variation by Trypanosoma brucei Telomere Proteins Depends on Their Unique DNA Binding Activities

Bibo Li et al.

Summary: Trypanosoma brucei regularly switches its major surface antigen to evade host immune response, with telomere and subtelomere structure integrity being crucial for its survival and pathogenesis. Telomere proteins TRF and RAP1, with unique nucleic acid binding activities, play key roles in VSG expression and switching. Targeting TbTRF and TbRAP1's nucleic acid binding activities may serve as a potential therapeutic strategy against T. brucei.

PATHOGENS (2021)

Article Biochemistry & Molecular Biology

Structure, interdomain dynamics, and pH-dependent autoactivation of pro-rhodesain, the main lysosomal cysteine protease from African trypanosomes

Patrick Johe et al.

Summary: The lysosomal cathepsin L-like cysteine protease in Trypanosoma brucei rhodesiense plays a crucial role in parasite proliferation, pathogenicity, and blood-brain barrier penetration. The presence of a unique alpha-helix in the prodomain and interdomain salt bridge dynamics are identified as key factors regulating enzyme activity and pH sensitivity.

JOURNAL OF BIOLOGICAL CHEMISTRY (2021)

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)

Review Pharmacology & Pharmacy

Flavonoid-derived Privileged Scaffolds in anti-Trypanosoma brucei Drug Discovery

Pone Kamdem Boniface et al.

CURRENT DRUG TARGETS (2019)

Review Chemistry, Medicinal

Folates in Trypanosoma brucei: Achievements and Opportunities

Gregorio Cullia et al.

CHEMMEDCHEM (2018)

Article Microbiology

The trypanocidal benzoxaborole AN7973 inhibits trypanosome mRNA processing

Daniela Begolo et al.

PLOS PATHOGENS (2018)

Article Biochemistry & Molecular Biology

Thiol redox biology of trypanosomatids and potential targets for chemotherapy

Alejandro E. Leroux et al.

MOLECULAR AND BIOCHEMICAL PARASITOLOGY (2016)

Review Pharmacology & Pharmacy

Bacterial, fungal and protozoan carbonic anhydrases as drug targets

Clemente Capasso et al.

EXPERT OPINION ON THERAPEUTIC TARGETS (2015)

Article Infectious Diseases

Genomic and Proteomic Studies on the Mode of Action of Oxaboroles against the African Trypanosome

Deuan C. Jones et al.

PLOS NEGLECTED TROPICAL DISEASES (2015)

Review Biochemistry & Molecular Biology

The unique chemistry of benzoxaboroles: Current and emerging applications in biotechnology and therapeutic treatments

C. Tony Liu et al.

BIOORGANIC & MEDICINAL CHEMISTRY (2014)

Review Parasitology

Nitro drugs for the treatment of trypanosomatid diseases: past, present, and future prospects

Stephen Patterson et al.

TRENDS IN PARASITOLOGY (2014)

Article Chemistry, Medicinal

Inhibition of Rhodesain as a Novel Therapeutic Modality for Human African Trypanosomiasis

Roberta Ettari et al.

JOURNAL OF MEDICINAL CHEMISTRY (2013)

Review Chemistry, Medicinal

Trypanocidal Activity of Marine Natural Products

Amy J. Jones et al.

MARINE DRUGS (2013)

Article Multidisciplinary Sciences

Discovery of a potent benzoxaborole-based anti-pneumococcal agent targeting leucyl-tRNA synthetase

Qing-Hua Hu et al.

SCIENTIFIC REPORTS (2013)

Review Plant Sciences

Natural Products As Sources of New Drugs over the 30 Years from 1981 to 2010

David J. Newman et al.

JOURNAL OF NATURAL PRODUCTS (2012)

Article Biochemistry & Molecular Biology

Nifurtimox Activation by Trypanosomal Type I Nitroreductases Generates Cytotoxic Nitrile Metabolites

Belinda S. Hall et al.

JOURNAL OF BIOLOGICAL CHEMISTRY (2011)

Review Biochemistry & Molecular Biology

Lipid metabolism in Trypanosoma brucei

Terry K. Smith et al.

MOLECULAR AND BIOCHEMICAL PARASITOLOGY (2010)

Editorial Material Multidisciplinary Sciences

Chagas disease: pushing through the pipeline

Julie Clayton

NATURE (2010)

Article Multidisciplinary Sciences

N-myristoyltransferase inhibitors as new leads to treat sleeping sickness

Julie A. Frearson et al.

NATURE (2010)

Article Parasitology

Lipidomic analysis of bloodstream and procyclic form Trypanosoma brucei

Gregory S. Richmond et al.

PARASITOLOGY (2010)

Article Microbiology

A Molecular Mechanism for Eflornithine Resistance in African Trypanosomes

Isabel M. Vincent et al.

PLOS PATHOGENS (2010)

Article Biochemistry & Molecular Biology

Vinyl Sulfones as Antiparasitic Agents and a Structural Basis for Drug Design

Iain D. Kerr et al.

JOURNAL OF BIOLOGICAL CHEMISTRY (2009)

Review Microbiology

Common strategies for antigenic variation by bacterial, fungal and protozoan pathogens

Kirk W. Deitsch et al.

NATURE REVIEWS MICROBIOLOGY (2009)

Review Medicine, General & Internal

Preferred Reporting Items for Systematic Reviews and Meta-Analyses: The PRISMA Statement

David Moher et al.

PLOS MEDICINE (2009)

Article Multidisciplinary Sciences

A mechanism for cross-resistance to nifurtimox and benznidazole in trypanosomes

Shane R. Wilkinson et al.

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (2008)

Article Multidisciplinary Sciences

Discovery of potent pteridine reductase inhibitors to guide antiparasite drug development

Antonio Cavazzuti et al.

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (2008)

Review Microbiology

Cytokinesis in trypanosomatilds

Tansy C. Hammarton et al.

CURRENT OPINION IN MICROBIOLOGY (2007)

Article Microbiology

A cysteine protease inhibitor cures Chagas' disease in an immunodeficient-mouse model of infection

Patricia S. Doyle et al.

ANTIMICROBIAL AGENTS AND CHEMOTHERAPY (2007)

Review Biochemistry & Molecular Biology

Cell cycle regulation in Trypanosoma brucei

Tansy C. Hammarton

MOLECULAR AND BIOCHEMICAL PARASITOLOGY (2007)

Review Biochemistry & Molecular Biology

Adaptations in the lipid metabolism of the protozoan parasite Trypanosoma brucei

Jaap J. van Hellemond et al.

FEBS LETTERS (2006)

Article Multidisciplinary Sciences

The genome of the kinetoplastid parasite, Leishmania major

AC Ivens et al.

SCIENCE (2005)

Article Multidisciplinary Sciences

The genome of the African trypanosome Trypanosoma brucei

M Berriman et al.

SCIENCE (2005)

Article Biochemistry & Molecular Biology

Trypanosome telomeres are protected by a homologue of mammalian TRF2

B Li et al.

MOLECULAR AND CELLULAR BIOLOGY (2005)

Article Biochemistry & Molecular Biology

Myristoyl-CoA:protein N-myristoyltransferase, an essential enzyme and potential drug target in kinetoplastid parasites

HP Price et al.

JOURNAL OF BIOLOGICAL CHEMISTRY (2003)