Comparative In Vitro Toxicology of Novel Cytoprotective Short-Chain Naphthoquinones
Short-chain quinones (SCQs) have been identified as potential drug candidates against mitochondrial dysfunction, which largely depends on the reversible redox characteristics of the active quinone core. We recently identified 11 naphthoquinone derivatives, <b>1</b>–<b>11,</b>...
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| Format: | Article |
| Language: | English |
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MDPI AG
2020-08-01
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| Series: | Pharmaceuticals |
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| Online Access: | https://www.mdpi.com/1424-8247/13/8/184 |
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| author | Zikai Feng Mohammed Sedeeq Abraham Daniel Monika Corban Krystel L. Woolley Ryan Condie Iman Azimi Jason A. Smith Nuri Gueven |
| author_facet | Zikai Feng Mohammed Sedeeq Abraham Daniel Monika Corban Krystel L. Woolley Ryan Condie Iman Azimi Jason A. Smith Nuri Gueven |
| author_sort | Zikai Feng |
| collection | DOAJ |
| description | Short-chain quinones (SCQs) have been identified as potential drug candidates against mitochondrial dysfunction, which largely depends on the reversible redox characteristics of the active quinone core. We recently identified 11 naphthoquinone derivatives, <b>1</b>–<b>11,</b> from a library of SCQs that demonstrated enhanced cytoprotection and improved metabolic stability compared to the clinically used benzoquinone idebenone. Since the toxicity properties of our promising SCQs were unknown, this study developed multiplex methods and generated detailed toxicity profiles from 11 endpoint measurements using the human hepatocarcinoma cell line HepG2. Overall, the toxicity profiles were largely comparable across different assays, with simple standard assays showing increased sensitivity compared to commercial toxicity assays. Within the 11 naphthoquinones tested, the <i><span style="font-variant: small-caps;">L</span></i>-phenylalanine derivative <b>4</b> consistently demonstrated the lowest toxicity across all assays. The results of this study not only provide useful information about the toxicity features of SCQs but will also enable the progression of the most promising drug candidates towards their clinical use. |
| first_indexed | 2024-03-10T17:50:11Z |
| format | Article |
| id | doaj.art-b63c65d3cc964dbda215c5111f54635e |
| institution | Directory Open Access Journal |
| issn | 1424-8247 |
| language | English |
| last_indexed | 2024-03-10T17:50:11Z |
| publishDate | 2020-08-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceuticals |
| spelling | doaj.art-b63c65d3cc964dbda215c5111f54635e2023-11-20T09:23:08ZengMDPI AGPharmaceuticals1424-82472020-08-0113818410.3390/ph13080184Comparative In Vitro Toxicology of Novel Cytoprotective Short-Chain NaphthoquinonesZikai Feng0Mohammed Sedeeq1Abraham Daniel2Monika Corban3Krystel L. Woolley4Ryan Condie5Iman Azimi6Jason A. Smith7Nuri Gueven8School of Pharmacy and Pharmacology, University of Tasmania, Hobart, TAS 7005, AustraliaSchool of Pharmacy and Pharmacology, University of Tasmania, Hobart, TAS 7005, AustraliaSchool of Pharmacy and Pharmacology, University of Tasmania, Hobart, TAS 7005, AustraliaSchool of Pharmacy and Pharmacology, University of Tasmania, Hobart, TAS 7005, AustraliaSchool of Natural Sciences, University of Tasmania, Hobart, TAS 7005, AustraliaSchool of Natural Sciences, University of Tasmania, Hobart, TAS 7005, AustraliaSchool of Pharmacy and Pharmacology, University of Tasmania, Hobart, TAS 7005, AustraliaSchool of Natural Sciences, University of Tasmania, Hobart, TAS 7005, AustraliaSchool of Pharmacy and Pharmacology, University of Tasmania, Hobart, TAS 7005, AustraliaShort-chain quinones (SCQs) have been identified as potential drug candidates against mitochondrial dysfunction, which largely depends on the reversible redox characteristics of the active quinone core. We recently identified 11 naphthoquinone derivatives, <b>1</b>–<b>11,</b> from a library of SCQs that demonstrated enhanced cytoprotection and improved metabolic stability compared to the clinically used benzoquinone idebenone. Since the toxicity properties of our promising SCQs were unknown, this study developed multiplex methods and generated detailed toxicity profiles from 11 endpoint measurements using the human hepatocarcinoma cell line HepG2. Overall, the toxicity profiles were largely comparable across different assays, with simple standard assays showing increased sensitivity compared to commercial toxicity assays. Within the 11 naphthoquinones tested, the <i><span style="font-variant: small-caps;">L</span></i>-phenylalanine derivative <b>4</b> consistently demonstrated the lowest toxicity across all assays. The results of this study not only provide useful information about the toxicity features of SCQs but will also enable the progression of the most promising drug candidates towards their clinical use.https://www.mdpi.com/1424-8247/13/8/184mitochondriashort-chain quinoneidebenonecytotoxicity |
| spellingShingle | Zikai Feng Mohammed Sedeeq Abraham Daniel Monika Corban Krystel L. Woolley Ryan Condie Iman Azimi Jason A. Smith Nuri Gueven Comparative In Vitro Toxicology of Novel Cytoprotective Short-Chain Naphthoquinones Pharmaceuticals mitochondria short-chain quinone idebenone cytotoxicity |
| title | Comparative In Vitro Toxicology of Novel Cytoprotective Short-Chain Naphthoquinones |
| title_full | Comparative In Vitro Toxicology of Novel Cytoprotective Short-Chain Naphthoquinones |
| title_fullStr | Comparative In Vitro Toxicology of Novel Cytoprotective Short-Chain Naphthoquinones |
| title_full_unstemmed | Comparative In Vitro Toxicology of Novel Cytoprotective Short-Chain Naphthoquinones |
| title_short | Comparative In Vitro Toxicology of Novel Cytoprotective Short-Chain Naphthoquinones |
| title_sort | comparative in vitro toxicology of novel cytoprotective short chain naphthoquinones |
| topic | mitochondria short-chain quinone idebenone cytotoxicity |
| url | https://www.mdpi.com/1424-8247/13/8/184 |
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