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

作　　者：Inga Eva Stik Lange Elisabeth Mieko Furusho Pral Anahi Magdaleno Ariel Mariano Silber 

机构地区：[1]Departamento de Parasitologia,Instituto de Ciencias,Universidade de Sao Paulo,Sao Paulo,Brazil

出　　处：《International Journal of Clinical Medicine》2012年第5期344-351,共8页临床医学国际期刊（英文）

基　　金：supported by grants from the Fundacao de Amparo a Pesquisa do Estado de Sao Paulo(FAPESP grant#11/50631-1 to AMS),Instituto Nacional de Biologia Estrutural e Química Medicinal em Doencas Infecciosas(INBEQMeDI);Conselho Nacional de Desenvolvimento Científico e Tecnológico(CNPq grant#470272/2011-2 to AMS).

摘　　要：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.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 

分 类 号：R73[医药卫生—肿瘤]