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Yang WY, Marrone SA, Minors N, et al. Fine-tuning alkyne cycloadditions: Insights into photochemistry responsible for the double-strand DNA cleavage via structural perturbations in diaryl alkyne conjugates. Beilstein J Org Chem. 2011;7:813-23doi: 10.3762/bjoc.7.93.
Yang, W. Y., Marrone, S. A., Minors, N., Zorio, D. A., & Alabugin, I. V. (2011). Fine-tuning alkyne cycloadditions: Insights into photochemistry responsible for the double-strand DNA cleavage via structural perturbations in diaryl alkyne conjugates. Beilstein journal of organic chemistry, 7813-23. https://doi.org/10.3762/bjoc.7.93
Yang, Wang-Yong, et al. "Fine-tuning alkyne cycloadditions: Insights into photochemistry responsible for the double-strand DNA cleavage via structural perturbations in diaryl alkyne conjugates." Beilstein journal of organic chemistry vol. 7 (2011): 813-23. doi: https://doi.org/10.3762/bjoc.7.93
Yang WY, Marrone SA, Minors N, Zorio DA, Alabugin IV. Fine-tuning alkyne cycloadditions: Insights into photochemistry responsible for the double-strand DNA cleavage via structural perturbations in diaryl alkyne conjugates. Beilstein J Org Chem. 2011;7:813-23. doi: 10.3762/bjoc.7.93. Epub 2011 Jun 16. PMID: 21804877; PMCID: PMC3135214.
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Beilstein J Org Chem. 2011;7:813-23. doi: 10.3762/bjoc.7.93. Epub 2011 Jun 16.

Fine-tuning alkyne cycloadditions: Insights into photochemistry responsible for the double-strand DNA cleavage via structural perturbations in diaryl alkyne conjugates.

Beilstein journal of organic chemistry

Wang-Yong Yang, Samantha A Marrone, Nalisha Minors, Diego A R Zorio, Igor V Alabugin

Affiliations

  1. Department of Chemistry and Biochemistry, Florida State University, Tallahassee, FL 32306-4390, USA.

PMID: 21804877 PMCID: PMC3135214 DOI: 10.3762/bjoc.7.93

Abstract

Hybrid molecules combining photoactivated aryl acetylenes and a dicationic lysine moiety cause the most efficient double-strand (ds) DNA cleavage known to date for a small molecule. In order to test the connection between the alkylating ability and the DNA-damaging properties of these compounds, we investigated the photoreactivity of three isomeric aryl-tetrafluoropyridinyl (TFP) alkynes with amide substituents in different positions (o-, m-, and p-) toward a model π-system. Reactions with 1,4-cyclohexadiene (1,4-CHD) were used to probe the alkylating properties of the triplet excited states in these three isomers whilst Stern-Volmer quenching experiments were used to investigate the kinetics of photoinduced electron transfer (PET). The three analogous isomeric lysine conjugates cleaved DNA with different efficiencies (34, 15, and 0% of ds DNA cleavage for p-, m-, and o-substituted lysine conjugates, respectively) consistent with the alkylating ability of the respective acetamides. The significant protecting effect of the hydroxyl radical and singlet oxygen scavengers to DNA cleavage was shown only with m-lysine conjugate. All three isomeric lysine conjugates inhibited human melanoma cell growth under photoactivation: The p-conjugate had the lowest CC(50) (50% cell cytotoxicity) value of 1.49 × 10(-7) M.

Keywords: DNA alkylation; cancer cell proliferation assay; lysine conjugate; photo-DNA cleavage; photocycloaddition; plasmid relaxation assay; triplet excitation

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