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Quinone methides : photochemical generation and antiproliferative activity

Quinone methides (QMs) are important intermediates in the chemistry of phenols. The interest in QMs was particularly intensified in the past decade due to their biological activity. Several classes of anticancer antibiotics base their antiproliferative action on metabolic formation of these transient species [1]. In the Laboratory for synthetic organic chemistry we have become interested in the photochemical formation of sterically congested QMs [2]. They are formed in the photodehydration reactions of 2-hydroxy-2-adamantylphenols (1). The sterical hindrance of the bulky adamantyl group makes the corresponding QMs particularly long-lived and selective in the reactions with nucleophiles. In continuation of the research, we have studied photochemical reactivity of a series of hydroxybiphenyls 2 and naphthalenes 3. The formation of QMs was confirmed in these examples by transient spectroscopy. In addition, we performed an investigation of antiproliferative activity of photogenerated QMs. We have shown that irradiation of cells treated with adamantyl derivative of 4-hydroxybiphenyl or 2-naphthol induce stronger antiproliferative activity than the nonirradiated samples. The research on photochemical generation of QMs was also extended to the reactions involving excited state intramolecular proton transfer (ESIPT) from the phenolic OH to the carbon atom of the adjacent phenyl ring. We have found an example of the most efficient protonation of carbon in the excited state ever reported [4]. Antiproliferative investigations indicated that irradiation of cells treated with anthracene 4 lead to enhanced activity, in accordance with the transient formation of QM in the ESIPT reaction.

Quinon-methides ; ESPIT reactions ; antiproliferative activity

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