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Evaluation of the Anti-Trypanosoma cruzi Effects of the Antipsychotic Drug Levomepromazine

International Journal of Clinical Medicine 2012年第5期3卷 344-351页

作者： Inga Eva Stik Lange Elisabeth Mieko Furusho Pral Anahi Magdaleno Ariel Mariano Silber Departamento de Parasitologia Instituto de CienciasUniversidade de Sao PauloSao PauloBrazil

Chagas disease, caused by the protozoan Trypanosoma cruzi, is a relevant parasitic disease in the Americas. Current chemotherapy relies on Nifurtimox and Benznidazole, which present serious drawbacks, including high toxicity, low efficiency and the emergence of resistant strains. In the present work, the perspectives of levomepromazine, a tri-cyclic compound belonging to the family of phenotiazines with well-known properties as antipsychotics were evaluated as a potential anti-T. cruzi drug. We show that this drug is able to inhibit the proliferation of epimastigotes (IC50 = 0.41 ± 0.01 mM) and to interfere with the infection of the host cells (IC50 = 0.34 ± 0.01 mM). Interestingly, the treatment with levomepromazine affected the ability of metabolites such as glucose, proline and glutamate to fuel the recovery of epi-mastigotes after being submitted to metabolic stress. These findings prompt levomepromazine as a promising leader drug to obtain new trypanocidal activities.

关键词： Chagas Disease Phenothiazines trypanothione reductase Amino Acid Metabolism Chemotherapy

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Challenges in the chemotherapy of Chagas disease: Looking for possibilities related to the differences and similarities between the parasite and host

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World Journal of Biological Chemistry 2017年第1期8卷 57-80页

作者： Vitor Sueth-Santiago Debora Decote-Ricardo Alexandre Morrot Celio Geraldo Freire-de-Lima Marco Edilson Freire Lima Instituto Federal de Educacao Ciência e Tecnologia do Rio de JaneiroCampus Sao Goncalo Universidade Federal Rural do Rio de Janeiro Instituto de Ciências ExatasDepartamento de Química Universidade Federal Rural do Rio de Janeiro Instituto de VeterináriaDepartamento de Microbiologia e Imunologia Veterinária Universidade Federal do Rio de Janeiro

Almost 110 years after the first studies by Dr. Carlos Chagas describing an infectious disease that was named for him, Chagas disease remains a neglected illness and a death sentence for infected people in poor countries. This short review highlights the enormous need for new studies aimed at the development of novel and more specific drugs to treat chagasic patients. The primary tool for facing this challenge is deep knowledge about the similarities and differences between the parasite and its human host.

关键词： Trypanosoma cruzi Trans-sialidase trypanothione reductase CYP51 Cruzipain Tubulin

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