Quinone Methide Alkylation of Deoxycytidine

Rokita, Steven E.; Yang, Jianhong; Pande, Praveen; Greenberg, William A.

doi:10.1021/jo9700336

Cited by 76 publications

(76 citation statements)

References 33 publications

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“…2 correspond to the anticipated sites of attack according to the published reactivity of the QMs with deoxynucleosides. [12][13][14][15] The reactivity of the photogenerated QM 2 was also investigated with amino acids. The irradiation of 1 in CH 3 CN-H 2 O was performed in the presence of C-protected glycine, serine and N-and C-protected cysteine.…”

Section: Resultsmentioning

confidence: 99%

Enhancement of antiproliferative activity by phototautomerization of anthrylphenols

Kralj

Uzelac

Wang

et al. 2015

Photochem Photobiol Sci

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An antiproliferative investigation was conducted on 3 human cancer cell lines, HCT 116 (colon), MCF-7 (breast), and H 460 (lung), on a series of 4 anthrylphenols in the dark and upon exposure to light (350 nm). 9-(2-Hydroxyphenyl)anthracene (1) moderately inhibited proliferation, but irradiation considerably enhanced the effect. The other anthracenes 4–6 exhibited antiproliferative activity in the dark, which was not enhanced upon irradiation. The enhancement of the antiproliferative effect on the irradiation of 1 was rationalized as being due to the formation of quinone methide (QM 2) by excited state proton transfer. QM 2 acts as an electrophilic species capable of reacting with biological molecules. Although QM 2 reacts with nucleotides, the adducts could not be isolated. On the contrary, cysteine adduct 8 was isolated and characterized, whereas the adducts with glycine, serine and tripeptide glutathione were characterized by MS. Non-covalent binding of 1 to DNA and bovine serum albumin was demonstrated by UV-vis, fluorescence and CD spectroscopy. However, a straightforward conclusion regarding the DNA or protein alkylating (damaging) ability of 2 could not be drawn. The results obtained by the irradiation of 1 in the presence of DNA, amino acids and peptides, cell cycle perturbation analysis, and in vitro translation of GFP suggest that the effect is not only due to the damage of DNA but also due to the impact on the cellular proteins. Considering that to date all QM agents were assumed to target DNA dominantly, this is an important finding with an impact on the further development of anticancer agents based on QMs.

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Section: Resultsmentioning

confidence: 99%

Enhancement of antiproliferative activity by phototautomerization of anthrylphenols

Kralj

Uzelac

Wang

et al. 2015

Photochem Photobiol Sci

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“…In competition experiments with the deoxymononucleosides, they found that the efficiency of cytosine modification was more than 10-fold than that of adensine and guanine. Their results indicated that guanine was the predominant target in duplex DNA like the selectivity of most natural products forming quinone methide-like species [54][55]. They gave the possible formation of the adducts between quinone methide and deoxynucleosides, which is shown in Figs.…”

Section: Q U I N O N E M E T H I D E S R E a C T W I T H Nucleobasesmentioning

confidence: 96%

Quinone Methide Derivatives: Important Intermediates to DNA Alkylating and DNA Cross-linking Actions

Wang

Song²,

Zhang³

et al. 2005

CMC

112

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Induced DNA interstrand cross-links by chemical agents or photoactivation play very important roles for cancer therapy. Several important clinical drugs (e.g. cisplatin, psoralens, and mitomycin C) are known to induce DNA ISC formation, which can disrupt cell maintenance and replication. Among these anti-tumor agents, one mechanism was involved in quinone methide intermediate. Quinone methide derivative has played important roles in organic syntheses as well as in chemical and biological processes. This review is concerned with current efforts of quinone methide derivatives to DNA alkylation and DNA cross-links. The latest advances in this field will be reviewed in this article. The chemical and physical properties of quinone methide derivatives, the interactions between nucleobases and quinone methide derivatives, the reactions with phosphodiester, DNA alkylation and cross-link via quinone methide intermediate action will be discussed.

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“…Similarly, BHT undergoes -oxidation to form a quinone-methide species (figure 38) [22]. This reactive electrophilic species acts as a Michael acceptor and binds covalently to the DNA bases similar to the quinones resulting in formation of adducts [197,222]. The BHT derived quinone-methides form adducts at the N 1 and N 2 positions of dG (table 8) as well as N 6 position of dA [219].…”

Section: Quinone-methidesmentioning

confidence: 99%

Influence of structural and functional modifications of selected genotoxic carcinogens on metabolism and mutagenicity – a review

Kulkarni

Moir

Zhu

2007

SAR and QSAR in Environmental Research

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Alterations in molecular structure are responsible for the differential biological response(s) of a chemical inside a biosystem. Structural and functional parameters that govern a chemical's metabolic course and determine its ultimate outcome in terms of mutagenic/carcinogenic potential are extensively reviewed here. A large number of environmentally-significant organic chemicals are addressed under one or more broadly classified groups each representing one or more characteristic structural feature. Numerous examples are cited to illustrate the influence of key structural and functional parameters on the metabolism and DNA adduction properties of different chemicals. It is hoped that, in the event of limited experimental data on a chemical's bioactivity, such knowledge of the likely roles played by key molecular features should provide preliminary information regarding its bioactivation, detoxification and/or mutagenic potential and aid the process of screening and prioritising chemicals for further testing.

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Quinone Methide Alkylation of Deoxycytidine

Cited by 76 publications

References 33 publications

Enhancement of antiproliferative activity by phototautomerization of anthrylphenols

Enhancement of antiproliferative activity by phototautomerization of anthrylphenols

Quinone Methide Derivatives: Important Intermediates to DNA Alkylating and DNA Cross-linking Actions

Influence of structural and functional modifications of selected genotoxic carcinogens on metabolism and mutagenicity – a review

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