Kim, Mi Kyoung Park, Kwang-Su Lee, Chaewoon Park, Hye Ri Choo, Hyunah Chong, Youhoon 2024-01-20T18:02:09Z 2024-01-20T18:02:09Z 2021-09-04 2010-12-23 0022-2623 https://pubs.kist.re.kr/handle/201004/130812 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. English AMER CHEMICAL SOC INDUCED GROWTH-INHIBITION LOW-DENSITY-LIPOPROTEIN IN-VITRO EVALUATION CELL-CULTURE MEDIA COLON-CANCER CELLS HYDROGEN-PEROXIDE ORAL BIOAVAILABILITY FLAVONOID QUERCETIN LIPID-PEROXIDATION ANTIVIRAL ACTIVITY Enhanced Stability and Intracellular Accumulation of Quercetin by Protection of the Chemically or Metabolically Susceptible Hydroxyl Groups with a Pivaloxymethyl (POM) Promoiety Article 10.1021/jm101252m 1 JOURNAL OF MEDICINAL CHEMISTRY, v.53, no.24, pp.8597 - 8607 JOURNAL OF MEDICINAL CHEMISTRY 53 24 8597 8607 scie scopus 000285264300013 2-s2.0-78650321830 Chemistry, Medicinal Pharmacology & Pharmacy Article INDUCED GROWTH-INHIBITION LOW-DENSITY-LIPOPROTEIN IN-VITRO EVALUATION CELL-CULTURE MEDIA COLON-CANCER CELLS HYDROGEN-PEROXIDE ORAL BIOAVAILABILITY FLAVONOID QUERCETIN LIPID-PEROXIDATION ANTIVIRAL ACTIVITY quercetin prodrug pivaloxymethyl (POM)