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Nucleic Acids as Therapeutic Targets and Agents
Published in David E. Thurston, Ilona Pysz, Chemistry and Pharmacology of Anticancer Drugs, 2021
The detailed mechanism of activation of mitomycin-C is complex (see Figure 5.38). It is thought that initial reduction of the quinone moiety (i.e., one-electron reduction yields a semiquinone, while two-electron reduction provides the hydroquinone) transforms the heterocyclic nitrogen from a conjugated amido to an amino form, thus making it more electron rich and facilitating elimination of the ring junction methoxy group. Tautomerization of the resulting iminium ion and loss of the carbamate group then creates an electrophilic center that is susceptible to nucleophilic attack by a DNA base. Nucleophilic attack on the aziridine moiety by a nucleophile on the opposite strand of DNA then occurs leading to an interstrand cross-link. The predominant adducts appear to form between two guanine C2-NH2 groups within the minor groove of DNA.
Drug Analysis of Protein Microspheres: From Pharmaceutical Preparation to In Vivo Fate
Published in Neville Willmott, John Daly, Microspheres and Regional Cancer Therapy, 2020
Jeffrey Cummings, David Watson, John F. Smyth
The unique structural backbone of the anthracyclines confers three general properties, which are the key to their in vivo pharmacology: The planar ring system and charged side chains enable high affinity noncovalent binding to DNA by a process termed “intercalation” in which the drug binds in parallel to the base pairs of DNA.The quinone moiety undergoes bioreduction to produce a semiquinone drug-free radical, which in turn can redox cycle with molecular oxygen to generate a cascade of reactive oxygen species.The quinone (C ring) and hydroquinone (B ring) moiety can chelate iron III.
Electron Spin Resonance Spectroscopy
Published in Adorjan Aszalos, Modern Analysis of Antibiotics, 2020
George C. Yang, Adorjan Aszalos
In biological environments, several enzymes can produce semiquinones from quinones, and the resultant semiquinones serve as one-electron carriers to oxygen [18,19]. Nonenzymatically, superoxides are produced via air oxidation of quinols to form semiquinones or, by the oxidation of semiquinone-free radical, assuming only one electron is transferred during the bimolecular collision [19,20].
The WHO claims estrogens are ‘carcinogenic’: is this true?
Published in Climacteric, 2023
The potential genotoxic effects of estrogen metabolites are not caused solely by the quinones (Figure 1(b)). Further intermediate metabolites are involved, especially ‘semiquinones’, which act within a reversible ‘redox-cycling’ together with the quinone as a stable complex, detectable using fluorescence spectroscopy [69–73] (Figure 2(a,b)). NADPH-dependent Cyt.B5 reductases (‘quinone reductases’) reduce the quinones to radical semiquinones (primarily a carcinoprotective mechanism to avoid action of quinones on DNA) which can also be produced directly from catecholestrogens by peroxidases. Thus, both oxidation and reduction proceed via the semiquinone intermediate. Semiquinone plus quinone can form a stable complex which can damage DNA and/or form DNA adducts with the potential to create gene mutations. Furthermore, the semiquinone intermediates can directly also react with molecular oxygen and form a superoxide anion, starting another detrimental reaction cascade which can lead to carcinogenic action.
A novel hepatoprotective activity of Alangium salviifolium in mouse model
Published in Drug and Chemical Toxicology, 2022
Preeti Dhruve, Mohd Nauman, Raosaheb K. Kale, Rana P. Singh
The specific activities of phase II enzymes DTD and GST, increased dose-dependently with BEA treatment above their respective basal levels. These enzymes are important detoxifier of carcinogens. GSTs catalyze the conjugation of reduced glutathiones to electrophilic and hydrophobic compound (Nakamura et al. 2000) and DTD functions to transfer two electrons to quinone giving the end product; hydroquinone. This avoids the formation of semiquinone and hence its accumulation which ultimately leads to oxidative stress and damage to the cells (Iyanagi and Yamazaki 1970). Hydroquinone formed is later conjugated to sulfate and glucuronide and finally excreted. Thus the significant enhancement in activity of these enzymes by BEA, as observed in the present study may contribute to its chemopreventive and hepatoprotective efficacy. When looking at the chemopreventive potential of a compound, phase II enzymes are mainly considered over the phase I enzymes.
Bioactivation of herbal constituents: mechanisms and toxicological relevance
Published in Drug Metabolism Reviews, 2019
Catechols and hydroquinones are readily oxidized to ortho- and para-quinones respectively by a variety of oxidative enzymes including P450s, peroxidase, tyrosinase, xanthine oxidase, monoamine oxidase, COX-2, and even metal ions (Bolton et al. 2000). Semiquinone radicals are initially formed via. one-electron oxidation along with ROS leading to oxidative stress. Depending on the prooxidant/antioxidant balance within cells, however, the catechols and hydroquinones can quench ROS protecting cells from oxidative stress.