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Screening for Small Molecule Modulators of Trypanosoma brucei Hsp70 Chaperone Activity Based upon Alcyonarian Coral-Derived Natural Products
The Trypanosoma brucei Hsp70/J-protein machinery plays an essential role in survival, differentiation, and pathogenesis of the protozoan parasite, and is an emerging target against African Trypanosomiasis. This study evaluated a set of small molecules, inspired by the malonganenones and nuttingins,...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7074166/ https://www.ncbi.nlm.nih.gov/pubmed/32012664 http://dx.doi.org/10.3390/md18020081 |
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author | Andreassend, Sarah K. Bentley, Stephen J. Blatch, Gregory L. Boshoff, Aileen Keyzers, Robert A. |
author_facet | Andreassend, Sarah K. Bentley, Stephen J. Blatch, Gregory L. Boshoff, Aileen Keyzers, Robert A. |
author_sort | Andreassend, Sarah K. |
collection | PubMed |
description | The Trypanosoma brucei Hsp70/J-protein machinery plays an essential role in survival, differentiation, and pathogenesis of the protozoan parasite, and is an emerging target against African Trypanosomiasis. This study evaluated a set of small molecules, inspired by the malonganenones and nuttingins, as modulators of the chaperone activity of the cytosolic heat inducible T. brucei Hsp70 and constitutive TbHsp70.4 proteins. The compounds were assessed for cytotoxicity on both the bloodstream form of T. b. brucei parasites and a mammalian cell line. The compounds were then investigated for their modulatory effect on the aggregation suppression and ATPase activities of the TbHsp70 proteins. A structure–activity relationship for the malonganenone-class of alkaloids is proposed based upon these results. |
format | Online Article Text |
id | pubmed-7074166 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-70741662020-03-19 Screening for Small Molecule Modulators of Trypanosoma brucei Hsp70 Chaperone Activity Based upon Alcyonarian Coral-Derived Natural Products Andreassend, Sarah K. Bentley, Stephen J. Blatch, Gregory L. Boshoff, Aileen Keyzers, Robert A. Mar Drugs Article The Trypanosoma brucei Hsp70/J-protein machinery plays an essential role in survival, differentiation, and pathogenesis of the protozoan parasite, and is an emerging target against African Trypanosomiasis. This study evaluated a set of small molecules, inspired by the malonganenones and nuttingins, as modulators of the chaperone activity of the cytosolic heat inducible T. brucei Hsp70 and constitutive TbHsp70.4 proteins. The compounds were assessed for cytotoxicity on both the bloodstream form of T. b. brucei parasites and a mammalian cell line. The compounds were then investigated for their modulatory effect on the aggregation suppression and ATPase activities of the TbHsp70 proteins. A structure–activity relationship for the malonganenone-class of alkaloids is proposed based upon these results. MDPI 2020-01-27 /pmc/articles/PMC7074166/ /pubmed/32012664 http://dx.doi.org/10.3390/md18020081 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Andreassend, Sarah K. Bentley, Stephen J. Blatch, Gregory L. Boshoff, Aileen Keyzers, Robert A. Screening for Small Molecule Modulators of Trypanosoma brucei Hsp70 Chaperone Activity Based upon Alcyonarian Coral-Derived Natural Products |
title | Screening for Small Molecule Modulators of Trypanosoma brucei Hsp70 Chaperone Activity Based upon Alcyonarian Coral-Derived Natural Products |
title_full | Screening for Small Molecule Modulators of Trypanosoma brucei Hsp70 Chaperone Activity Based upon Alcyonarian Coral-Derived Natural Products |
title_fullStr | Screening for Small Molecule Modulators of Trypanosoma brucei Hsp70 Chaperone Activity Based upon Alcyonarian Coral-Derived Natural Products |
title_full_unstemmed | Screening for Small Molecule Modulators of Trypanosoma brucei Hsp70 Chaperone Activity Based upon Alcyonarian Coral-Derived Natural Products |
title_short | Screening for Small Molecule Modulators of Trypanosoma brucei Hsp70 Chaperone Activity Based upon Alcyonarian Coral-Derived Natural Products |
title_sort | screening for small molecule modulators of trypanosoma brucei hsp70 chaperone activity based upon alcyonarian coral-derived natural products |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7074166/ https://www.ncbi.nlm.nih.gov/pubmed/32012664 http://dx.doi.org/10.3390/md18020081 |
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