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Biological activity of photochemically generated quinone methides

Quinone methides (QM) are important reactive intermediates in chemistry of phenols that have attracted scientific attention owing to their biological activity [1]. Some classes of antitumor antibiotics exert their action on metabolic formation of QMs that alkylate DNA molecules. Photochemical reactions of suitably substituted phenols represent particularly applicable method for the QM generation in biological systems since they are conducted under mild conditions and enable spatial and temporal control of the process [2]. Several classes of phenols 1 [3], hydoxybiphenyls 2 [4], naphthols 3 [5] and anthracene derivatives 4, 5 [6], were synthesized and their photochemical reactivity investigated. Antiproliferative activity of the photogenerated QMs was evaluated on three tumor cancer cell lines (colon HCT 116, breast MCF-7, and lung H 460), with and without exposure of cells to UV-vis irradiation. The investigation indicated lead molecules that exhibit enhanced activity on exposure to irradiation. The mechanism of the antiproliferative action was studied for the selected molecules by performing investigation of non-covalent binding to DNA, irradiations of plasmid DNA in the presence of compound, followed by the analysis by alkaline gel electrophoresis, and a study of cell cycle. The experiments indicated that photogenerated QMs do not only react with DNA, but probably inhibit some intracellular enzymes. These findings open new possibilities in the design of compounds for anticancer phototherapy based on photogeneration of QMs.

Quinone methides (QM) ; hydoxybiphenyls ; naphthols ; anthracene derivatives ; photochemistry ; photogenerated QMs

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