Phototoxicity of 7-oxycoumarins with keratinocytes in culture

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 C 3-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 concentrationdependent alteration in migration on neutral gels caused by nicking was observed.

Exploring the Potential of Supercritical Fluid Extraction of Matricaria chamomilla White Ray Florets as a Source of Bioactive (Cosmetic) Ingredients

“…Simultaneously, several studies also reveal the potentially negative effects of coumarin and its derivatives on skin. These compounds have irritating and phototoxic activities [82,83]. This is in line with our findings: extracts with higher coumarin content (FAF10, FAF12) showed greater cytotoxicity and phototoxicity.…”

Natural Coumarins: Exploring the Pharmacological Complexity and Underlying Molecular Mechanisms

“…Due to their photosensitizing properties, 6, 7-furano-coumarins are contraindicated in case of prolonged exposure to sunlight, due to the risk of photodermatitis, burns, and melanomas [ 153 ]. Doses of coumarin in a human's daily diet were calculated at 0.02 mg/bw, and the concentration of coumarin varies from 1 m/bw in celery to 7000 mg/bw in Ceylon cinnamon and over 87000 mg/bw in Cassia cinnamon.…”