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Metabolic stability of new mito-protective short-chain naphthoquinones
Citation
Feng, Z and Smith, JA and Gueven, N and Quirino, JP, Metabolic stability of new mito-protective short-chain naphthoquinones, Pharmaceuticals, 13, (2) pp. 1-12. ISSN 1424-8247 (2020) [Refereed Article]
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Copyright Statement
Copyright 2020 The Authors. Licensed under Creative Commons Attribution 4.0 International (CC BY 4.0) https://creativecommons.org/licenses/by/4.0/
Abstract
Short-chain quinones (SCQs) have been identified as potential drug candidates against
mitochondrial dysfunction, which is largely dependent on their reversible redox characteristics of the
active quinone core. We recently synthesized a SCQ library of > 148 naphthoquinone derivatives and
identified 16 compounds with enhanced cytoprotection compared to the clinically used benzoquinone
idebenone. One of the major drawbacks of idebenone is its high metabolic conversion in the liver, which
significantly restricts its therapeutic activity. Therefore, this study assessed the metabolic stability of
the 16 identified naphthoquinone derivatives 1–16 using hepatocarcinoma cells in combination with
an optimized reverse-phase liquid chromatography (RP-LC) method. Most of the derivatives showed
significantly better stability than idebenone over 6 hours (p < 0.001). By extending the side-chain
of SCQs, increased stability for some compounds was observed. Metabolic conversion from the
derivative 3 to 5 and reduced idebenone metabolism in the presence of 5 were also observed. These
results highlight the therapeutic potential of naphthoquinone-based SCQs and provide essential
insights for future drug design, prodrug therapy and polytherapy, respectively.
Item Details
| Item Type: | Refereed Article |
|---|---|
| Keywords: | mitochondrial dysfunction, idebenone, short-chain quinone, metabolic stability, HepG2 cell culture, reverse-phase liquid chromatography |
| Research Division: | Biomedical and Clinical Sciences |
| Research Group: | Pharmacology and pharmaceutical sciences |
| Research Field: | Pharmaceutical sciences |
| Objective Division: | Manufacturing |
| Objective Group: | Human pharmaceutical products |
| Objective Field: | Human pharmaceutical treatments |
| UTAS Author: | Feng, Z (Mr Zikai Feng) |
| UTAS Author: | Smith, JA (Dr Jeremy Smith) |
| UTAS Author: | Gueven, N (Dr Nuri Guven) |
| UTAS Author: | Quirino, JP (Associate Professor Lito Quirino) |
| ID Code: | 137761 |
| Year Published: | 2020 |
| Web of Science® Times Cited: | 5 |
| Deposited By: | Pharmacy |
| Deposited On: | 2020-03-03 |
| Last Modified: | 2021-02-12 |
| Downloads: | 13 View Download Statistics |
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