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Comparative in vitro toxicology of novel cytoprotective short-chain naphthoquinones

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Feng, Z, Sedeeq, M, Daniel, AO ORCID: 0000-0002-3650-7837, Corban, M, Woolley, KL, Condie, R, Azimi, I ORCID: 0000-0001-9477-9999, Smith, JA ORCID: 0000-0001-6313-3298 and Gueven, N ORCID: 0000-0003-3782-767X 2020 , 'Comparative in vitro toxicology of novel cytoprotective short-chain naphthoquinones' , Pharmaceuticals, vol. 13, no. 8 , pp. 1-20 , doi: 10.3390/ph13080184.

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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, 1–11, 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 Type: Article
Authors/Creators:Feng, Z and Sedeeq, M and Daniel, AO and Corban, M and Woolley, KL and Condie, R and Azimi, I and Smith, JA and Gueven, N
Keywords: mitochondrial dysfunction, short-chain quinones, drug discovery, cytotoxicity, mitochondria
Journal or Publication Title: Pharmaceuticals
Publisher: MDPI
ISSN: 1424-8247
DOI / ID Number: 10.3390/ph13080184
Copyright Information:

© 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/).

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