Screening for small molecule modulators of Trypanosoma brucei Hsp70 chaperone activity based upon alcyonarian coral-derived natural products
- Andreassend, Sarah K, Bentley, Stephen, Blatch, Gregory L, Boshoff, Aileen, Keyzers, Robert A
- Authors: Andreassend, Sarah K , Bentley, Stephen , Blatch, Gregory L , Boshoff, Aileen , Keyzers, Robert A
- Date: 2020
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/426045 , vital:72309 , xlink:href="https://doi.org/10.3390/md18020081"
- 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.
- Full Text:
- Date Issued: 2020
- Authors: Andreassend, Sarah K , Bentley, Stephen , Blatch, Gregory L , Boshoff, Aileen , Keyzers, Robert A
- Date: 2020
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/426045 , vital:72309 , xlink:href="https://doi.org/10.3390/md18020081"
- 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.
- Full Text:
- Date Issued: 2020
Anti-oesophageal cancer activity in extracts of deep-water Marion Island sponges
- Davies-Coleman, Michael T, Froneman, P William, Keyzers, Robert A, Whibley, Catherine, Hendricks, Denver T, Samaai, Toufiek, McQuaid, Christopher D
- Authors: Davies-Coleman, Michael T , Froneman, P William , Keyzers, Robert A , Whibley, Catherine , Hendricks, Denver T , Samaai, Toufiek , McQuaid, Christopher D
- Date: 2005
- Language: English
- Type: Article
- Identifier: vital:6569 , http://hdl.handle.net/10962/d1004132
- Description: Oesophageal cancer is one of the most common causes of cancer-related deaths in South African black males. The limited efficacy of chemotherapeutic agents to treat this disease has prompted a search for potential new chemical entities with anticancer properties. We report here on the evidence for anti-oesophageal cancer activity in the methanolic extracts of five species of sponges dredged from a depth of approximately 100 m in the vicinity of Marion Island in the Southern Ocean during the autumn of 2004.
- Full Text:
- Date Issued: 2005
- Authors: Davies-Coleman, Michael T , Froneman, P William , Keyzers, Robert A , Whibley, Catherine , Hendricks, Denver T , Samaai, Toufiek , McQuaid, Christopher D
- Date: 2005
- Language: English
- Type: Article
- Identifier: vital:6569 , http://hdl.handle.net/10962/d1004132
- Description: Oesophageal cancer is one of the most common causes of cancer-related deaths in South African black males. The limited efficacy of chemotherapeutic agents to treat this disease has prompted a search for potential new chemical entities with anticancer properties. We report here on the evidence for anti-oesophageal cancer activity in the methanolic extracts of five species of sponges dredged from a depth of approximately 100 m in the vicinity of Marion Island in the Southern Ocean during the autumn of 2004.
- Full Text:
- Date Issued: 2005
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