The Trypanocidal Activity of Amidine Compounds Does Not Correlate with Their Binding Affinity to Trypanosoma cruzi Kinetoplast DNA
| Autor(a) principal: | |
|---|---|
| Data de Publicação: | 2011 |
| Outros Autores: | , , , , , , , , , , , , , , , |
| Tipo de documento: | Artigo |
| Idioma: | eng |
| Título da fonte: | Repositório Institucional da FIOCRUZ (ARCA) |
| Texto Completo: | https://www.arca.fiocruz.br/handle/icict/15908 |
Resumo: | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biologia Celular. Rio de Janeiro, RJ, Brasil. |
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Daliry, A.Pires, M. Q.Silva, C. F.Pacheco, R. S.Munde, M.Stephens, C. E.Kumar, A.Ismail, M. A.Liu, Z.Farahat, A. A.Akay, SenolSom, P.Hu, Q.Boykin, D. W.Wilson, W. D.Castro, S. L. deSoeiro, M. N. C.2016-09-22T13:44:10Z2016-09-22T13:44:10Z2011DALIRY, 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. 2011.0066-4804https://www.arca.fiocruz.br/handle/icict/159081098-6596engAmerican Society for MicrobiologyTrypanosoma cruziDoença de ChagasDNA do cinetoplastoAmidinasAtividade tripanocidaTrypanosoma cruziChagas Diseasekinetoplast DNAAmidinesTrypanocidal ActivityThe Trypanocidal Activity of Amidine Compounds Does Not Correlate with Their Binding Affinity to Trypanosoma cruzi Kinetoplast DNAinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleFundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biologia Celular. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Sistemática Bioquímica. 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 Sistemática Bioquímica. Rio de Janeiro, RJ, Brasil.Georgia State University. Department of Chemistry. Atlanta, GA, USA.Georgia State University. Department of Chemistry. Atlanta, GA, USA.Georgia State University. Department of Chemistry. Atlanta, GA, USA.Georgia State University. Department of Chemistry. Atlanta, GA, USA.Georgia State University. Department of Chemistry. Atlanta, GA, USA.Georgia State University. Department of Chemistry. Atlanta, GA, USA.Georgia State University. Department of Chemistry. Atlanta, GA, USA.Georgia State University. Department of Chemistry. Atlanta, GA, USA.Georgia State University. Department of Chemistry. Atlanta, GA, USA.Georgia State University. Department of Chemistry. Atlanta, GA, USA.Georgia State University. Department of Chemistry. Atlanta, GA, USA.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.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.info:eu-repo/semantics/openAccessreponame:Repositório Institucional da FIOCRUZ (ARCA)instname:Fundação Oswaldo Cruz (FIOCRUZ)instacron:FIOCRUZLICENSElicense.txtlicense.txttext/plain; charset=utf-82991https://www.arca.fiocruz.br/bitstream/icict/15908/1/license.txt5a560609d32a3863062d77ff32785d58MD51ORIGINALa_daliry_etal_IOC_2011.pdfa_daliry_etal_IOC_2011.pdfapplication/pdf1961866https://www.arca.fiocruz.br/bitstream/icict/15908/2/a_daliry_etal_IOC_2011.pdfeadbfe7f822c077e8b85bcfa68123d03MD52TEXTa_daliry_etal_IOC_2011.pdf.txta_daliry_etal_IOC_2011.pdf.txtExtracted texttext/plain39542https://www.arca.fiocruz.br/bitstream/icict/15908/3/a_daliry_etal_IOC_2011.pdf.txt21a3d84daa5265dc59cf8149ec7ba899MD53icict/159082018-06-05 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| dc.title.pt_BR.fl_str_mv |
The Trypanocidal Activity of Amidine Compounds Does Not Correlate with Their Binding Affinity to Trypanosoma cruzi Kinetoplast DNA |
| title |
The Trypanocidal Activity of Amidine Compounds Does Not Correlate with Their Binding Affinity to Trypanosoma cruzi Kinetoplast DNA |
| spellingShingle |
The Trypanocidal Activity of Amidine Compounds Does Not Correlate with Their Binding Affinity to Trypanosoma cruzi Kinetoplast DNA Daliry, A. Trypanosoma cruzi Doença de Chagas DNA do cinetoplasto Amidinas Atividade tripanocida Trypanosoma cruzi Chagas Disease kinetoplast DNA Amidines Trypanocidal Activity |
| title_short |
The Trypanocidal Activity of Amidine Compounds Does Not Correlate with Their Binding Affinity to Trypanosoma cruzi Kinetoplast DNA |
| title_full |
The Trypanocidal Activity of Amidine Compounds Does Not Correlate with Their Binding Affinity to Trypanosoma cruzi Kinetoplast DNA |
| title_fullStr |
The Trypanocidal Activity of Amidine Compounds Does Not Correlate with Their Binding Affinity to Trypanosoma cruzi Kinetoplast DNA |
| title_full_unstemmed |
The Trypanocidal Activity of Amidine Compounds Does Not Correlate with Their Binding Affinity to Trypanosoma cruzi Kinetoplast DNA |
| title_sort |
The Trypanocidal Activity of Amidine Compounds Does Not Correlate with Their Binding Affinity to Trypanosoma cruzi Kinetoplast DNA |
| author |
Daliry, A. |
| author_facet |
Daliry, A. Pires, M. Q. Silva, C. F. Pacheco, R. S. Munde, M. Stephens, C. E. Kumar, A. Ismail, M. A. Liu, Z. Farahat, A. A. Akay, Senol Som, P. Hu, Q. Boykin, D. W. Wilson, W. D. Castro, S. L. de Soeiro, M. N. C. |
| author_role |
author |
| author2 |
Pires, M. Q. Silva, C. F. Pacheco, R. S. Munde, M. Stephens, C. E. Kumar, A. Ismail, M. A. Liu, Z. Farahat, A. A. Akay, Senol Som, P. Hu, Q. Boykin, D. W. Wilson, W. D. Castro, S. L. de Soeiro, M. N. C. |
| author2_role |
author author author author author author author author author author author author author author author author |
| dc.contributor.author.fl_str_mv |
Daliry, A. Pires, M. Q. Silva, C. F. Pacheco, R. S. Munde, M. Stephens, C. E. Kumar, A. Ismail, M. A. Liu, Z. Farahat, A. A. Akay, Senol Som, P. Hu, Q. Boykin, D. W. Wilson, W. D. Castro, S. L. de Soeiro, M. N. C. |
| dc.subject.other.pt_BR.fl_str_mv |
Trypanosoma cruzi Doença de Chagas DNA do cinetoplasto Amidinas Atividade tripanocida |
| topic |
Trypanosoma cruzi Doença de Chagas DNA do cinetoplasto Amidinas Atividade tripanocida Trypanosoma cruzi Chagas Disease kinetoplast DNA Amidines Trypanocidal Activity |
| dc.subject.en.pt_BR.fl_str_mv |
Trypanosoma cruzi Chagas Disease kinetoplast DNA Amidines Trypanocidal Activity |
| description |
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biologia Celular. Rio de Janeiro, RJ, Brasil. |
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2011 |
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2011 |
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2016-09-22T13:44:10Z |
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2016-09-22T13:44:10Z |
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info:eu-repo/semantics/publishedVersion |
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info:eu-repo/semantics/article |
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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. |
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https://www.arca.fiocruz.br/handle/icict/15908 |
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0066-4804 |
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1098-6596 |
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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. 0066-4804 1098-6596 |
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American Society for Microbiology |
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American Society for Microbiology |
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