| Author | Daliry, A. | |
| Author | Pires, M. Q. | |
| Author | Silva, C. F. | |
| Author | Pacheco, R. S. | |
| Author | Munde, M. | |
| Author | Stephens, C. E. | |
| Author | Kumar, A. | |
| Author | Ismail, M. A. | |
| Author | Liu, Z. | |
| Author | Farahat, A. A. | |
| Author | Akay, Senol | |
| Author | Som, P. | |
| Author | Hu, Q. | |
| Author | Boykin, D. W. | |
| Author | Wilson, W. D. | |
| Author | Castro, S. L. de | |
| Author | Soeiro, M. N. C. | |
| Access date | 2016-09-22T13:44:10Z | |
| Available date | 2016-09-22T13:44:10Z | |
| Document date | 2011 | |
| Citation | DALIRY, A. et al. The Trypanocidal Activity of Amidine Compounds Does Not Correlate with Their Binding Affinity to Trypanosoma cruzi Kinetoplast DNA. Antimicrobial Agents and Chemotherapy, v. 55, n. 10, p. 4765-4773, Oct. 2011. | pt_BR |
| ISSN | 0066-4804 | pt_BR |
| URI | https://www.arca.fiocruz.br/handle/icict/15908 | |
| Language | eng | pt_BR |
| Publisher | American Society for Microbiology | pt_BR |
| Rights | open access | |
| Subject in Portuguese | Trypanosoma cruzi | pt_BR |
| Subject in Portuguese | Doença de Chagas | pt_BR |
| Subject in Portuguese | DNA do cinetoplasto | pt_BR |
| Subject in Portuguese | Amidinas | pt_BR |
| Subject in Portuguese | Atividade tripanocida | pt_BR |
| Title | The Trypanocidal Activity of Amidine Compounds Does Not Correlate with Their Binding Affinity to Trypanosoma cruzi Kinetoplast DNA | pt_BR |
| Type | Article | |
| Abstract | Due to limited efficacy and considerable toxicity, the therapy for Chagas’ disease is far from being ideal,
and thus new compounds are desirable. Diamidines and related compounds such as arylimidamides have
promising trypanocidal activity against Trypanosoma cruzi. To better understand the mechanism of action
of these heterocyclic cations, we investigated the kinetoplast DNA (kDNA) binding properties and trypanocidal
efficacy against T. cruzi of 13 compounds. Four diamidines (DB75, DB569, DB1345, and DB829),
eight arylimidamides (DB766, DB749, DB889, DB709, DB613, DB1831, DB1852, and DB2002), and one
guanylhydrazone (DB1080) were assayed in thermal denaturation (Tm) and circular dichroism (CD)
studies using whole purified T. cruzi kDNA and a conserved synthetic parasite sequence. The overall CD
spectra using the whole kDNA were similar to those found for the conserved sequence and were indicative
of minor groove binding. Our findings showed that some of the compounds that exhibited the highest
trypanocidal activities (e.g., DB766) caused low or no change in the Tm measurements. However, while
some active compounds, such as DB766, induced profound alterations of kDNA topology, others, like
DB1831, although effective, did not result in altered Tm and CD measurements. Our data suggest that the
strong affinity of amidines with kDNA per se is not sufficient to generate and trigger their trypanocidal
activity. Cell uptake differences and possibly distinct cellular targets need to be considered in the final
evaluation of the mechanisms of action of these compounds. | pt_BR |
| Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biologia Celular. Rio de Janeiro, RJ, Brasil. | pt_BR |
| Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Sistemática Bioquímica. Rio de Janeiro, RJ, Brasil. | pt_BR |
| Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biologia Celular. Rio de Janeiro, RJ, Brasil. | pt_BR |
| Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Sistemática Bioquímica. Rio de Janeiro, RJ, Brasil. | pt_BR |
| Affilliation | Georgia State University. Department of Chemistry. Atlanta, GA, USA. | pt_BR |
| Affilliation | Georgia State University. Department of Chemistry. Atlanta, GA, USA. | pt_BR |
| Affilliation | Georgia State University. Department of Chemistry. Atlanta, GA, USA. | pt_BR |
| Affilliation | Georgia State University. Department of Chemistry. Atlanta, GA, USA. | pt_BR |
| Affilliation | Georgia State University. Department of Chemistry. Atlanta, GA, USA. | pt_BR |
| Affilliation | Georgia State University. Department of Chemistry. Atlanta, GA, USA. | pt_BR |
| Affilliation | Georgia State University. Department of Chemistry. Atlanta, GA, USA. | pt_BR |
| Affilliation | Georgia State University. Department of Chemistry. Atlanta, GA, USA. | pt_BR |
| Affilliation | Georgia State University. Department of Chemistry. Atlanta, GA, USA. | pt_BR |
| Affilliation | Georgia State University. Department of Chemistry. Atlanta, GA, USA. | pt_BR |
| Affilliation | Georgia State University. Department of Chemistry. Atlanta, GA, USA. | pt_BR |
| Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biologia Celular. Rio de Janeiro, RJ, Brasil. | pt_BR |
| Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biologia Celular. Rio de Janeiro, RJ, Brasil. | pt_BR |
| Subject | Trypanosoma cruzi | pt_BR |
| Subject | Chagas Disease | pt_BR |
| Subject | kinetoplast DNA | pt_BR |
| Subject | Amidines | pt_BR |
| Subject | Trypanocidal Activity | pt_BR |
| e-ISSN | 1098-6596 | |
| xmlui.metadata.dc.subject.ods | 03 Saúde e Bem-Estar | |
