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[摘要]：In order to increase stability of quercetin, its metabolically and chemically susceptible hydroxyl groups 7-OH and 3-OH respectively were transiently blocked with a pivaloxymethyl (POM) promoiety to provide two novel quercetin conjugates [7-O-POM-Q (2), 3-O-POM-Q (3)]. In the absence of stabilizer (ascorbic acid), the synthesized conjugates showed significantly increased stability in cell culture media [t(1/2) = 4 h (2), 52 h (3)] compared with quercetin (t(1/2) < 30 min) and quercetin prodrug 1 (t(1/2) = 0.8 h). In addition, the quercetin conjugate 2 underwent efficient cellular uptake and intracellular levels of its hydrolysis product, quercetin, were maintained up to 12 h. Stability and intracellular accumulation of 2 were demonstrated by its stabilizer-independent cytostatic effect and induction of apoptotic cell death. Even though 3 was more stable than 2, it failed to penetrate cell membranes. However, the remarkable stability of 3 warrants further investigation of quercetin conjugates with various promoieties at the 3-OH position. |
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