Screening for Small Molecule Modulators of <i>Trypanosoma brucei</i> Hsp70 Chaperone Activity Based upon Alcyonarian Coral-Derived Natural Products
The <i>Trypanosoma brucei</i> 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 malonganenon...
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| Format: | Article |
| Language: | English |
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MDPI AG
2020-01-01
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| Series: | Marine Drugs |
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| Online Access: | https://www.mdpi.com/1660-3397/18/2/81 |
| _version_ | 1798039895016472576 |
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| author | Sarah K. Andreassend Stephen J. Bentley Gregory L. Blatch Aileen Boshoff Robert A. Keyzers |
| author_facet | Sarah K. Andreassend Stephen J. Bentley Gregory L. Blatch Aileen Boshoff Robert A. Keyzers |
| author_sort | Sarah K. Andreassend |
| collection | DOAJ |
| description | The <i>Trypanosoma brucei</i> 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 <i>T. brucei</i> Hsp70 and constitutive TbHsp70.4 proteins. The compounds were assessed for cytotoxicity on both the bloodstream form of <i>T. b. brucei</i> 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. |
| first_indexed | 2024-04-11T21:59:59Z |
| format | Article |
| id | doaj.art-f2d5dde257474f11b9769f7e0758f5de |
| institution | Directory Open Access Journal |
| issn | 1660-3397 |
| language | English |
| last_indexed | 2024-04-11T21:59:59Z |
| publishDate | 2020-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Marine Drugs |
| spelling | doaj.art-f2d5dde257474f11b9769f7e0758f5de2022-12-22T04:00:58ZengMDPI AGMarine Drugs1660-33972020-01-011828110.3390/md18020081md18020081Screening for Small Molecule Modulators of <i>Trypanosoma brucei</i> Hsp70 Chaperone Activity Based upon Alcyonarian Coral-Derived Natural ProductsSarah K. Andreassend0Stephen J. Bentley1Gregory L. Blatch2Aileen Boshoff3Robert A. Keyzers4School of Chemical and Physical Sciences, Victoria University of Wellington, Wellington 6012, New ZealandBiotechnology Innovation Centre, Rhodes University, Grahamstown 6140, South AfricaBiomedical Biotechnology Research Unit, Department of Biochemistry and Microbiology, Grahamstown 6140, South AfricaBiotechnology Innovation Centre, Rhodes University, Grahamstown 6140, South AfricaSchool of Chemical and Physical Sciences, Victoria University of Wellington, Wellington 6012, New ZealandThe <i>Trypanosoma brucei</i> 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 <i>T. brucei</i> Hsp70 and constitutive TbHsp70.4 proteins. The compounds were assessed for cytotoxicity on both the bloodstream form of <i>T. b. brucei</i> 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.https://www.mdpi.com/1660-3397/18/2/81anti-parasiticheat shock proteinmalonganenonesarafrican trypanosomiasis |
| spellingShingle | Sarah K. Andreassend Stephen J. Bentley Gregory L. Blatch Aileen Boshoff Robert A. Keyzers Screening for Small Molecule Modulators of <i>Trypanosoma brucei</i> Hsp70 Chaperone Activity Based upon Alcyonarian Coral-Derived Natural Products Marine Drugs anti-parasitic heat shock protein malonganenone sar african trypanosomiasis |
| title | Screening for Small Molecule Modulators of <i>Trypanosoma brucei</i> Hsp70 Chaperone Activity Based upon Alcyonarian Coral-Derived Natural Products |
| title_full | Screening for Small Molecule Modulators of <i>Trypanosoma brucei</i> Hsp70 Chaperone Activity Based upon Alcyonarian Coral-Derived Natural Products |
| title_fullStr | Screening for Small Molecule Modulators of <i>Trypanosoma brucei</i> Hsp70 Chaperone Activity Based upon Alcyonarian Coral-Derived Natural Products |
| title_full_unstemmed | Screening for Small Molecule Modulators of <i>Trypanosoma brucei</i> Hsp70 Chaperone Activity Based upon Alcyonarian Coral-Derived Natural Products |
| title_short | Screening for Small Molecule Modulators of <i>Trypanosoma brucei</i> Hsp70 Chaperone Activity Based upon Alcyonarian Coral-Derived Natural Products |
| title_sort | screening for small molecule modulators of i trypanosoma brucei i hsp70 chaperone activity based upon alcyonarian coral derived natural products |
| topic | anti-parasitic heat shock protein malonganenone sar african trypanosomiasis |
| url | https://www.mdpi.com/1660-3397/18/2/81 |
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