Phototoxicity of 7-oxycoumarins with keratinocytes in culture
| Autor: | Keith Kardos, Christophe Guillon, Ned D. Heindel, Ivan Jabin, Michele M. Jetter, Thomas M. Mariano, Whittemore Marilyn S, Robert D. Rapp, Diane E. Heck, Yi Hua Jan, Jeffrey D. Laskin, Eric K. Akyea |
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| Rok vydání: | 2019 |
| Předmět: |
Keratinocytes
Biochimie Pharmacologie 01 natural sciences Biochemistry Article Phototoxicity chemistry.chemical_compound Mice Structure-Activity Relationship Plasmid Psoralens Coumarins Furocoumarins Drug Discovery 7-hydroxycoumarins medicine 7-oxycoumarins Animals DNA photo-damage Molecular Biology Cells Cultured Cell Proliferation Photosensitizing Agents Dose-Response Relationship Drug Molecular Structure 010405 organic chemistry Cell growth Methoxsalen Organic Chemistry Biologie moléculaire 8-MOP PAM212 keratinocytes Photochemical Processes Pyrone 0104 chemical sciences 010404 medicinal & biomolecular chemistry Chimie organique medicine.anatomical_structure chemistry Lipophilicity Biophysics Polar effect Keratinocyte medicine.drug |
| Zdroj: | Bioorg Chem Bioorganic chemistry, 89 |
| ISSN: | 1090-2120 |
| Popis: | Seventy-one 7-oxycoumarins, 66 synthesized and 5 commercially sourced, were tested for their ability to inhibit growth in murine PAM212 keratinocytes. Forty-nine compounds from the library demonstrated light-induced lethality. None was toxic in the absence of UVA light. Structure-activity correlations indicate that the ability of the compounds to inhibit cell growth was dependent not only on their physiochemical characteristics, but also on their ability to absorb UVA light. Relative lipophilicity was an important factor as was electron density in the pyrone ring. Coumarins with electron withdrawing moieties – cyano and fluoro at C3 – were considerably less active while those with bromines or iodine at that location displayed enhanced activity. Coumarins that were found to inhibit keratinocyte growth were also tested for photo-induced DNA plasmid nicking. A concentration-dependent alteration in migration on neutral gels caused by nicking was observed. SCOPUS: ar.j info:eu-repo/semantics/published |
| Databáze: | OpenAIRE |
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