Naphthoquinones Oxidize H₂S to Polysulfides and Thiosulfate, Implications for Therapeutic Applications.

Content Provider	Europe PMC
Author	Olson, Kenneth R. Clear, Kasey J. Derry, Paul J. Gao, Yan Ma, Zhilin Cieplik, Nathaniel M. Fiume, Alyssa Gaziano, Dominic J. Kasko, Stephen M. Narloch, Kathleen Velander, Cecilia L. Nwebube, Ifeyinwa Pallissery, Collin J. Pfaff, Ella Villa, Brian P. Kent, Thomas A. Wu, Gang Straub, Karl D.
Editor	Nakamaru-Ogiso, Eiko
Copyright Year	2022
Abstract	1,4-Napththoquinones (NQs) are clinically relevant therapeutics that affect cell function through production of reactive oxygen species (ROS) and formation of adducts with regulatory protein thiols. Reactive sulfur species (RSS) are chemically and biologically similar to ROS and here we examine RSS production by NQ oxidation of hydrogen sulfide (H2S) using RSS-specific fluorophores, liquid chromatography-mass spectrometry, UV-Vis absorption spectrometry, oxygen-sensitive optodes, thiosulfate-specific nanoparticles, HPLC-monobromobimane derivatization, and ion chromatographic assays. We show that NQs, catalytically oxidize H2S to per- and polysulfides (H2Sn, n = 2−6), thiosulfate, sulfite and sulfate in reactions that consume oxygen and are accelerated by superoxide dismutase (SOD) and inhibited by catalase. The approximate efficacy of NQs (in decreasing order) is, 1,4-NQ ≈ juglone ≈ plumbagin > 2-methoxy-1,4-NQ ≈ menadione >> phylloquinone ≈ anthraquinone ≈ menaquinone ≈ lawsone. We propose that the most probable reactions are an initial two-electron oxidation of H2S to S0 and reduction of NQ to NQH2. S0 may react with H2S or elongate H2Sn in variety of reactions. Reoxidation of NQH2 likely involves a semiquinone radical (NQ·−) intermediate via several mechanisms involving oxygen and comproportionation to produce NQ and superoxide. Dismutation of the latter forms hydrogen peroxide which then further oxidizes RSS to sulfoxides. These findings provide the chemical background for novel sulfur-based approaches to naphthoquinone-directed therapies.
Journal	International Journal of Molecular Sciences [Int J Mol Sci]
Volume Number	23
DOI	10.3390/ijms232113293
PubMed Central reference number	PMC9657496
Issue Number	21
PubMed reference number	36362080
e-ISSN	14220067
Language	English
Publisher	Molecular Diversity Preservation International (MDPI)
Publisher Date	2022-10-31
Access Restriction	Open
Subject Keyword	reactive sulfur species reactive oxygen species antioxidants juglone plumbagin vitamin K
Content Type	Text
Resource Type	Article
Subject	Physical and Theoretical Chemistry Molecular Biology Spectroscopy Catalysis Computer Science Applications Medicine Inorganic Chemistry Organic Chemistry