engleski

Photochemical generation of long-lived quinone methides by deamination of p-cresol derivatives

Quinone methides (QM) are associated to the biological activity of numerous natural and syn- thetic compounds, as anticancer drugs, or mechanism-based enzyme inactivators. Appropriately substituted bifunctional QMs can cross-link molecules such as DNA or peptides and proteins. Since the formation of alkylating agents can be carried out under mild conditions (e.g. after irradiation), it opens up the possibility for the use in biological systems. Photoinduced DNA interstrand cross-linking can disrupt cell maintenance and replication, and therefore QMs play very important role in anticancer therapy. Within the on-going interest in our laboratory in photochemical formation of QMs and their antiproliferative activity, we have prepared QM precursors 1 and 2 and their hydrochloride salts 1HCl and 2HCl. Herein we report on photochemical reactivity of these derivatives, which was studied by preparative irradiations, laser flash photolysis (LFP) and fluorescence measurements. QMs were detected by LFP and the rate constants in the reactions with nucleophiles were determined. We have demonstrated that the attack of nucleophiles to QM2 generates new QM species. Such reactivity is of particular importance in biological systems since it enables the ultimate formation of the thermodynamically most stabile products in the reactions with DNA.

quinone methides; photochemistry; biological activity

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