- Title
- Sarqaquinoic acid and related synthetic naphthoquinones inhibit the function of Hsp90
- Creator
- Chiwakata, M, de la Mare, Jo-Anne, Edkins, Adrienne L, Beukes, Denzil R
- Date
- 2016
- Type
- text
- Type
- article
- Identifier
- http://hdl.handle.net/10962/66324
- Identifier
- vital:28933
- Identifier
- https://doi.org/10.1055/s-0036-1596751
- Description
- publisher version
- Description
- Heat shock protein 90 (Hsp90) is of critical importance in the proper folding of numerous proteins, including those involved in cancer. Consequently, there is significant interest in the discovery and development of Hsp90 inhibitors as anticancer drugs. In this study, we investigated the ability of sargaquinoic acid (SQA) and selected naphthoquinone derivatives to inhibit Hsp90 function. SQA was isolated and purified from Sargassum incisifolium while the naphthoquinones were synthesised via a straightforward sequence incorporating a Diels-Alder reaction between benzoquinone derivatives and myrcene followed by coupling with substituted alkyl or arylamines. Hsp90 inhibition was assessed by a client protein degradation assay. At a concentration of 1µM, SQA showed almost complete inhibition of Hsp90 but only moderate antiproliferative effects (IC50 658µM) against a Hs578T breast cancer carcinoma cell line. Interestingly, the most potent synthetic aminonaphthoquinone inhibited Hsp90 function by 50% at a concentration of 1µM but showed much improved activity against the Hs578T cell line (IC50 0.32µM). Furthermore, unlike geldanamycin, none of the compounds tested upregulates Hsp70 suggesting that these compounds may bind to the C-terminal end of Hsp90.
- Format
- Publisher
- Georg Thieme Verlag KG
- Language
- English
- Relation
- Planta Medica, Chiwakata,M., de la Mare,J-A ., Edkins, A., Beukes, D.R.(2016) Sarqaquinoic acid and related synthetic naphthoquinones inhibit the function of Hsp90. Planta Medica, 82 (S 01): p.702.https://doi.org/10.1055/s-0036-1596751, Planta Medica volume 82 number S01 702 702 2016 0032-0943
- Rights
- Thieme Planta Medica
- Rights
- Use of this resource is governed by the terms and conditions of the Thieme Authors’ rights and Green Open Access Statement (https://www.thieme.de/statics/dokumente/thieme/final/de/dokumente/sw_ autorenlounge/Autorenrechte_und_Hinweise_zum_Green_Open_Access_2016.pdf)
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Beukes, Denzil Ronwynne (Prof)
RU DST/NRF SARChI for Molecular and Cellular Biology of the Eukaryotic Stress Response
De la Mare, Jo-Anne (Dr)
Edkins, Adrienne Lesley (Associate Prof)
RU Department of Biochemistry, Microbiology and Bioinformatics
SDG 03. Good Health and Well-Being
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