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Comparative in vitro toxicology of novel cytoprotective short-chain naphthoquinones

Citation

Feng, Z and Sedeeq, M and Daniel, A and Corban, M and Woolley, KL and Condie, R and Azimi, I and Smith, JA and Gueven, N, Comparative in vitro toxicology of novel cytoprotective short-chain naphthoquinones, Pharmaceuticals, 13, (8) pp. 1-20. ISSN 1424-8247 (2020) [Refereed Article]


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Copyright Statement

2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).

DOI: doi:10.3390/ph13080184

Abstract

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, 111, 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 L-phenylalanine derivative 4 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.

Item Details

Item Type:Refereed Article
Keywords:mitochondrial dysfunction, short-chain quinones, drug discovery, cytotoxicity, mitochondria
Research Division:Biomedical and Clinical Sciences
Research Group:Pharmacology and pharmaceutical sciences
Research Field:Pharmaceutical sciences
Objective Division:Health
Objective Group:Clinical health
Objective Field:Clinical health not elsewhere classified
UTAS Author:Feng, Z (Mr Zikai Feng)
UTAS Author:Sedeeq, M (Mr Mohammed Sedeeq)
UTAS Author:Daniel, A (Mr Abraham Daniel)
UTAS Author:Corban, M (Ms Monika Corban)
UTAS Author:Woolley, KL (Miss Krystel Woolley)
UTAS Author:Condie, R (Mr Ryan Condie)
UTAS Author:Azimi, I (Dr Iman Azimi)
UTAS Author:Smith, JA (Associate Professor Jason Smith)
UTAS Author:Gueven, N (Dr Nuri Guven)
ID Code:140624
Year Published:2020
Web of Science® Times Cited:2
Deposited By:Pharmacy
Deposited On:2020-08-31
Last Modified:2021-03-04
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