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Expression Analysis of Thirteen Genes in Response to Nifurtimox and Benznidazole in Mexican Isolates of Trypanosoma cruzi by Digital PCR.
Acta Parasitol
January 2025
Edificio D, Facultad de Ciencias Químicas, LADISER Inmunología y Biología Molecular, Universidad Veracruzana, Orizaba, Veracruz, México.
Despite being the most relevant and critical option for managing Chagas disease, pharmacological therapy is currently limited by the availability of only two drugs, benznidazole and nifurtimox. Their effectiveness is further restricted in the chronic phase of the infection, as they induce severe side effects and require prolonged treatment. Additionally, the use of these drugs can lead to the emergence of substantial resistance problems, compounded by the potential natural resistance of some parasite isolates.
View Article and Find Full Text PDFSystem-based insights into parasitological and clinical treatment failure in Chagas disease.
mSystems
January 2025
Department of Chemistry and Biochemistry, San Diego State University, San Diego, California, USA.
Infectious disease treatment success requires symptom resolution (clinical treatment success), which often but not always involves pathogen clearance. Both of these treatment goals face disease-specific and general challenges. In this review, we summarize the current state of knowledge in mechanisms of clinical and parasitological treatment failure in the context of Chagas disease, a neglected tropical disease causing cardiac and gastrointestinal symptoms.
View Article and Find Full Text PDFTransforming the chemotherapy of human African trypanosomiasis.
Clin Microbiol Rev
January 2025
School of Infection and Immunity, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, United Kingdom.
SUMMARYPrior to 2019, when the orally available drug fexinidazole began its clinical use, the treatment of human African trypanosomiasis (HAT) was complex and unsatisfactory for many reasons. Two sub-species of the parasite are responsible for HAT, namely the rhodesiense form found in East and Southern Africa and the gambiense form found in Central and West Africa. Diseases caused by both forms manifest in two stages: stage 1 before and stage 2 after central nervous system involvement.
View Article and Find Full Text PDFOligostyrylbenzene Derivatives with Antiparasitic and Antibacterial Activity as Potent G-Quadruplex Ligands.
Molecules
December 2024
Departamento de Bioquímica y Farmacología Molecular, Instituto de Parasitología y Biomedicina López Neyra, CSIC, PTS Granada, Avenida del Conocimiento 17, 18016 Armilla, Spain.
G-quadruplexes (G4s) are non-canonical secondary structures that play a crucial role in the regulation of genetic expression. This study explores the interaction between G4s and a small family of oligostyrylbenzene (OSB) derivatives, characterized by tris(styryl)benzene and tetrastyrylbenzene backbones, functionalized with either trimethylammonium or 1-methylpyridinium groups. Initially identified as DNA ligands, these OSB derivatives have now been recognized as potent G4 binders, surpassing in binding affinity commercially available ligands such as pyridostatin and displaying good selectivity for G4s over duplex DNA.
View Article and Find Full Text PDFCationic and anionic PLGA-cholesterol hybrid nanoparticles as promising platforms to enhance the trypanocidal efficacy of benznidazole and drug delivery in Trypanosoma cruzi-infected cells.
Biomed Pharmacother
January 2025
Laboratory of Pharmaceutical Technology and Biotechnology, Department of Pharmacy, Federal University of Rio Grande do Norte-UFRN, Natal, RN, Brazil. Electronic address:
Chagas disease is a neglected tropical disease caused by the protozoan Trypanosoma cruzi, remains a significant global health challenge. Currently, benznidazole (BNZ) is the primary treatment in many countries. However, this drug is limited by low bioavailability, significant host toxicity, and reduced efficacy in chronic disease phase.
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