Please use this identifier to cite or link to this item: https://www.arca.fiocruz.br/handle/icict/11902
Title: Effect of 9-hydroxy-- and 7-hydroxy--pyran Naphthoquinones on Trypanosoma Cruzi and Structure-activity Relationship Studies
Authors: Rocha, David R. da
Souza, Alessandra M. T.
Souza, Ana Carolina G. de
Castro, Helena C.
Rodrigues, Carlos R.
Menna-Barreto, Rubem F. S.
Castro, Solange L. de
Ferreira, Vitor F.
Affilliation: Universidade Federal Fluminense. Instituto de Química. Departamento de Química Orgânica. Niterói, RJ, Brasil.
Universidade Federal do Rio de Janeiro. Faculdade de Farmácia. ModMolQSAR. Rio de Janeiro, RJ, Brasil.
Universidade Federal Fluminense. Instituto de Química. Departamento de Química Orgânica. Niterói, RJ, Brasil.
Universidade Federal Fluminense. Instituto de Biologia. Departamento de Biologia Celular e Molecular. LABioMol. Niterói, RJ, Brasil.
Universidade Federal do Rio de Janeiro. Faculdade de Farmácia. ModMolQSAR. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biologia Celular. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biologia Celular. Rio de Janeiro, RJ, Brasil.
Universidade Federal Fluminense. Instituto de Química. Departamento de Química Orgânica. Niterói, RJ, Brasil.
Abstract: The available treatment for the prevention and cure of Chagas disease, caused by the protozoan Trypanosoma cruzi, is still unsatisfactory. Thus, there is an urgent need to develop new drugs. In the last few years, our research group has focused on finding a new chemical entity able to target the infectious bloodstream trypomastigotes. In this study, we assayed 16 -lapachone analogous with modifications in the pyran and aromatic ring to find a new prototype with high trypanocidal activity. Interestingly, two ortho-naphthoquinones presented the best trypanocidal profile (8c and 8d with an IC50/24 h of 26.9 ± 1.3 and 23.5 ± 2.5 M, respectively), which were 4 to 17 times more effective than -lapachone (391.5 ± 16.5 M) and the standard drug benznidazole (103.6 ± 0.6 M). The introduction of a hydroxyl group on the compounds’ aromatic ring modulated their biological profile by increasing their activity not only for cancer cells (MDAMB435), as previously described in literature, but also against T. cruzi. The Structure-Activity Relationship (SAR) study indicated that this introduction modulated HOMO and MEP parameters, improving the trypanocidal activity.
Keywords: Pyran naphthoquinone
Trypanosoma cruzi
Chagas Disease
Chemotherapy
SAR
Molecular modeling
DeCS: Trypanosoma cruzi
Doença de Chagas
Quimioterapia
Saralasina
Issue Date: 2014
Publisher: Bentham Science Publishers
Citation: ROCHA, David R. da; et al. Effect of 9-hydroxy-- and 7-hydroxy--pyran Naphthoquinones on Trypanosoma Cruzi and Structure-activity Relationship Studies. Medicinal Chemistry, v.10,n.999, p.564-570, 2014.
ISSN: 1875-6638
Copyright: restricted access
Appears in Collections:IOC - Artigos de Periódicos

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