Single- and Two-Electron Reduction of Nitroaromatic Compounds by Flavoenzymes: Mechanisms and Implications for Cytotoxicity
Nitroaromatic compounds (ArNO<sub>2</sub>) maintain their importance in relation to industrial processes, environmental pollution, and pharmaceutical application. The manifestation of toxicity/therapeutic action of nitroaromatics may involve their single- or two-electron reduction perfor...
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| Format: | Article |
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MDPI AG
2021-08-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/22/16/8534 |
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| author | Narimantas Čėnas Aušra Nemeikaitė-Čėnienė Lidija Kosychova |
| author_facet | Narimantas Čėnas Aušra Nemeikaitė-Čėnienė Lidija Kosychova |
| author_sort | Narimantas Čėnas |
| collection | DOAJ |
| description | Nitroaromatic compounds (ArNO<sub>2</sub>) maintain their importance in relation to industrial processes, environmental pollution, and pharmaceutical application. The manifestation of toxicity/therapeutic action of nitroaromatics may involve their single- or two-electron reduction performed by various flavoenzymes and/or their physiological redox partners, metalloproteins. The pivotal and still incompletely resolved questions in this area are the identification and characterization of the specific enzymes that are involved in the bioreduction of ArNO<sub>2</sub> and the establishment of their contribution to cytotoxic/therapeutic action of nitroaromatics. This review addresses the following topics: (i) the intrinsic redox properties of ArNO<sub>2</sub>, in particular, the energetics of their single- and two-electron reduction in aqueous medium; (ii) the mechanisms and structure-activity relationships of reduction in ArNO<sub>2</sub> by flavoenzymes of different groups, dehydrogenases-electrontransferases (NADPH:cytochrome P-450 reductase, ferredoxin:NADP(H) oxidoreductase and their analogs), mammalian NAD(P)H:quinone oxidoreductase, bacterial nitroreductases, and disulfide reductases of different origin (glutathione, trypanothione, and thioredoxin reductases, lipoamide dehydrogenase), and (iii) the relationships between the enzymatic reactivity of compounds and their activity in mammalian cells, bacteria, and parasites. |
| first_indexed | 2024-03-10T08:45:42Z |
| format | Article |
| id | doaj.art-43613c5860274a25afbac924edd4f9d0 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T08:45:42Z |
| publishDate | 2021-08-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-43613c5860274a25afbac924edd4f9d02023-11-22T07:56:36ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-08-012216853410.3390/ijms22168534Single- and Two-Electron Reduction of Nitroaromatic Compounds by Flavoenzymes: Mechanisms and Implications for CytotoxicityNarimantas Čėnas0Aušra Nemeikaitė-Čėnienė1Lidija Kosychova2Institute of Biochemistry of Vilnius University, Saulėtekio 7, LT-10257 Vilnius, LithuaniaState Research Institute Center for Innovative Medicine, Santariškių St. 5, LT-08406 Vilnius, LithuaniaInstitute of Biochemistry of Vilnius University, Saulėtekio 7, LT-10257 Vilnius, LithuaniaNitroaromatic compounds (ArNO<sub>2</sub>) maintain their importance in relation to industrial processes, environmental pollution, and pharmaceutical application. The manifestation of toxicity/therapeutic action of nitroaromatics may involve their single- or two-electron reduction performed by various flavoenzymes and/or their physiological redox partners, metalloproteins. The pivotal and still incompletely resolved questions in this area are the identification and characterization of the specific enzymes that are involved in the bioreduction of ArNO<sub>2</sub> and the establishment of their contribution to cytotoxic/therapeutic action of nitroaromatics. This review addresses the following topics: (i) the intrinsic redox properties of ArNO<sub>2</sub>, in particular, the energetics of their single- and two-electron reduction in aqueous medium; (ii) the mechanisms and structure-activity relationships of reduction in ArNO<sub>2</sub> by flavoenzymes of different groups, dehydrogenases-electrontransferases (NADPH:cytochrome P-450 reductase, ferredoxin:NADP(H) oxidoreductase and their analogs), mammalian NAD(P)H:quinone oxidoreductase, bacterial nitroreductases, and disulfide reductases of different origin (glutathione, trypanothione, and thioredoxin reductases, lipoamide dehydrogenase), and (iii) the relationships between the enzymatic reactivity of compounds and their activity in mammalian cells, bacteria, and parasites.https://www.mdpi.com/1422-0067/22/16/8534nitroaromatic compoundsflavoenzymescytotoxicityoxidative stressbioreductive activation |
| spellingShingle | Narimantas Čėnas Aušra Nemeikaitė-Čėnienė Lidija Kosychova Single- and Two-Electron Reduction of Nitroaromatic Compounds by Flavoenzymes: Mechanisms and Implications for Cytotoxicity International Journal of Molecular Sciences nitroaromatic compounds flavoenzymes cytotoxicity oxidative stress bioreductive activation |
| title | Single- and Two-Electron Reduction of Nitroaromatic Compounds by Flavoenzymes: Mechanisms and Implications for Cytotoxicity |
| title_full | Single- and Two-Electron Reduction of Nitroaromatic Compounds by Flavoenzymes: Mechanisms and Implications for Cytotoxicity |
| title_fullStr | Single- and Two-Electron Reduction of Nitroaromatic Compounds by Flavoenzymes: Mechanisms and Implications for Cytotoxicity |
| title_full_unstemmed | Single- and Two-Electron Reduction of Nitroaromatic Compounds by Flavoenzymes: Mechanisms and Implications for Cytotoxicity |
| title_short | Single- and Two-Electron Reduction of Nitroaromatic Compounds by Flavoenzymes: Mechanisms and Implications for Cytotoxicity |
| title_sort | single and two electron reduction of nitroaromatic compounds by flavoenzymes mechanisms and implications for cytotoxicity |
| topic | nitroaromatic compounds flavoenzymes cytotoxicity oxidative stress bioreductive activation |
| url | https://www.mdpi.com/1422-0067/22/16/8534 |
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