NYMC Faculty Publications
Phototoxicity of 7-Oxycoumarins With Keratinocytes in Culture
DOI
10.1016/j.bioorg.2019.103014
Journal Title
Bioorganic Chemistry
First Page
103014
Document Type
Article
Publication Date
8-1-2019
Department
Environmental Health Science
Abstract
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.
Recommended Citation
Guillon, C., Jan, Y., Heck, D., Mariano, T., Rapp, R., Jetter, M., Kardos, K., Whittemore, M., Akyea, E., Jabin, I., Laskin, J., & Heindel, N. (2019). Phototoxicity of 7-Oxycoumarins With Keratinocytes in Culture. Bioorganic Chemistry, 89, 103014. https://doi.org/10.1016/j.bioorg.2019.103014
