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Special Issue "Bioreductive Activation/Detoxification of Prooxidant Xenobiotics and Drugs 2021"

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Role of Xenobiotics".

Deadline for manuscript submissions: closed (31 December 2021) | Viewed by 610

Special Issue Editor

Prof. Dr. Narimantas K. Cenas
E-Mail Website
Guest Editor
Institute of Biochemistry of Vilnius University, Saulėtekio 7, LT-10257 Vilnius, Lithuania
Interests: flavoenzyme catalysis; quinones; nitroaromatics; aromatic N-oxides; polyphenolic antioxidants; mechanisms of cytotoxicity
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Special Issue Information

Dear Colleagues,

Quinones, nitroaromatic compounds, and aromatic N-oxides represent important groups of anticancer, antimicrobial, and antiparasitic agents used with variable success. Additionally, nitroaromatics comprise an important group of industrial pollutants and are widely used as explosives. Importantly, the therapeutic activity and cytotoxicity or side-action of the above groups of compounds are most frequently attributed to their single- or two-electron reduction, performed mainly by flavoenzymes or low-potential FeS redox proteins. Depending on the reaction mechanism and the presence of reductively activated alkylating or leaving groups, bioreductive events may either confer cytotoxicity to the above compounds by means of oxidative stress or formation of alkylating products or contribute to their detoxification. Interestingly, similar bioreductive events occur at the initial steps of nitroaromatic pollutants’ biodegradation.

The diversification of cancer chemotherapy and tumor imaging methods and the emergence of parasite strains resistant to classical drugs require the permanent synthesis of new representatives of these compounds and studies of their mechanisms of action. The same applies for the design of new methods of biodegradation of prooxidant pollutants.

The aim of this Special Issue is to provide an updated point of view about the enzymatic mechanisms of single- and two-electron reduction of quinones, nitroaromatic compounds, aromatic N-oxides, and other groups of prooxidant compounds, their possible enzymatic targets, their role(s) in compound cytotoxicity or therapeutic activity, and their biodegradation efficiency.

Prof. Dr. Narimantas K. Cenas
Guest Editor

Manuscript Submission Information

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Keywords

  • prooxidant xenobiotics and drugs
  • free radicals
  • oxidative stress
  • bioreductive activation and alkylation
  • biodegradation

Published Papers (1 paper)

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Research

Article
Reactions of Recombinant Neuronal Nitric Oxide Synthase with Redox Cycling Xenobiotics: A Mechanistic Study
Int. J. Mol. Sci. 2022, 23(2), 980; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms23020980 - 17 Jan 2022
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Abstract
Neuronal nitric oxide synthase (nNOS) catalyzes single-electron reduction of quinones (Q), nitroaromatic compounds (ArNO2) and aromatic N-oxides (ArN → O), and is partly responsible for their oxidative stress-type cytotoxicity. In order to expand a limited knowledge on the enzymatic mechanisms [...] Read more.
Neuronal nitric oxide synthase (nNOS) catalyzes single-electron reduction of quinones (Q), nitroaromatic compounds (ArNO2) and aromatic N-oxides (ArN → O), and is partly responsible for their oxidative stress-type cytotoxicity. In order to expand a limited knowledge on the enzymatic mechanisms of these processes, we aimed to disclose the specific features of nNOS in the reduction of such xenobiotics. In the absence or presence of calmodulin (CAM), the reactivity of Q and ArN → O increases with their single-electron reduction midpoint potential (E17). ArNO2 form a series with lower reactivity. The calculations according to an “outer-sphere” electron transfer model show that the binding of CAM decreases the electron transfer distance from FMNH2 to quinone by 1–2 Å. The effects of ionic strength point to the interaction of oxidants with a negatively charged protein domain close to FMN, and to an increase in accessibility of the active center induced by high ionic strength. The multiple turnover experiments of nNOS show that, in parallel with reduced FAD-FMN, duroquinone reoxidizes the reduced heme, in particular its Fe2+-NO form. This finding may help to design the heme-targeted bioreductively activated agents and contribute to the understanding of the role of P-450-type heme proteins in the bioreduction of quinones and other prooxidant xenobiotics. Full article
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