Enhanced Stability and Intracellular Accumulation of Quercetin by Protection of the Chemically or Metabolically Susceptible Hydroxyl Groups with a Pivaloxymethyl (POM) Promoiety
- Enhanced Stability and Intracellular Accumulation of Quercetin by Protection of the Chemically or Metabolically Susceptible Hydroxyl Groups with a Pivaloxymethyl (POM) Promoiety
- 김미경; 박광수; 이채운; 박혜리; 추현아; 정유훈
- quercetin; prodrug; pivaloxymethyl (POM)
- Issue Date
- Journal of medicinal chemistry
- VOL 53, 8597-8607
- 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
[t1/2=4h (2), 52 h (3)] compared with quercetin (t1/2<30 min) and quercetin prodrug 1 (t1/2=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
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