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I. Stolic, K. Miskovic, A. Magdaleno, A. M. Silber, I. Piantanida, M. Bajic and L. Glavas-Obrovac "Effect of 3,4-ethylenedioxy-extension of thiophene core on the DNA/RNA binding properties and biological activity of bis-benzimidazole amidines". Bioorganic and Medicinal Chemistry, Vol. 17, 2009, pp. 2544-2554.

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• TITLE: Evaluation of the Anti-Trypanosoma Cruzi Effects of the Antipsychotic Drug Levomepromazine

  AUTHORS: Inga Eva Stik Lange, Elisabeth Mieko Furusho Pral, Anahí Magdaleno, Ariel Mariano Silber

  KEYWORDS: Chagas Disease; Phenothiazines; Trypanothione Reductase; Amino Acid Metabolism; Chemotherapy

  JOURNAL NAME: International Journal of Clinical Medicine, Vol.3 No.5, September 24, 2012

  ABSTRACT: 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.