Preprint Article Version 1 This version is not peer-reviewed

Metabolic Stability of New Mito-Protective Short-Chain Naphthoquinones

Version 1 : Received: 4 December 2019 / Approved: 5 December 2019 / Online: 5 December 2019 (03:56:02 CET)

How to cite: Feng, Z.; Smith, J.A.; Gueven, N.; Quirino, J.P. Metabolic Stability of New Mito-Protective Short-Chain Naphthoquinones. Preprints 2019, 2019120058 (doi: 10.20944/preprints201912.0058.v1). Feng, Z.; Smith, J.A.; Gueven, N.; Quirino, J.P. Metabolic Stability of New Mito-Protective Short-Chain Naphthoquinones. Preprints 2019, 2019120058 (doi: 10.20944/preprints201912.0058.v1).

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 is 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.

Subject Areas

mitochondrial dysfunction; idebenone; short-chain quinone; metabolic stability; HepG2 cell culture; reverse-phase liquid chromatography

Comments (0)

We encourage comments and feedback from a broad range of readers. See criteria for comments and our diversity statement.

Leave a public comment
Send a private comment to the author(s)
Views 0
Downloads 0
Comments 0
Metrics 0


×
Alerts
Notify me about updates to this article or when a peer-reviewed version is published.