title: Enhanced stability and intracellular accumulation of quercetin by protection of the chemically or metabolically susceptible hydroxyl groups with a pivaloxymethyl (POM) promoiety.
abstract: 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, 3-O-POM-Q]. In the absence of stabilizer (ascorbic acid), the synthesized conjugates showed significantly increased stability in cell culture media [t(½) = 4 h, 52 h] compared with quercetin (t(½) < 30 min) and quercetin prodrug 1 (t(½) = 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 were demonstrated by its stabilizer-independent cytostatic effect and induction of apoptotic cell death. Even though was more stable than, it failed to penetrate cell membranes. However, the remarkable stability of warrants further investigation of quercetin conjugates with various promoieties at the 3-OH position.
authors.affiliation: Department of Bioscience and Biotechnology, Bio/Molecular Informatics Center, Konkuk University, Seoul 143-701, Korea.
authors.forename: Mi Kyoung
authors.initials: MK
authors.lastname: Kim
authors.forename: Kwang-Su
authors.initials: KS
authors.lastname: Park
authors.forename: Chaewoon
authors.initials: C
authors.lastname: Lee
authors.forename: Hye Ri
authors.initials: HR
authors.lastname: Park
authors.forename: Hyunah
authors.initials: H
authors.lastname: Choo
authors.forename: Youhoon
authors.initials: Y
authors.lastname: Chong
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D002463:Cell Membrane Permeability; D002470:Cell Survival / Q000187:drug effects; D003470:Culture Media; D004354:Drug Screening Assays, Antitumor; D004355:Drug Stability; D006801:Humans; D006868:Hydrolysis; D011355:Prodrugs / Q000138:chemical synthesis* / Q000494:pharmacology; D011794:Quercetin / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000494:pharmacology; D012995:Solubility; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
chemical_list: C555219:3-O-pivaloxymethylquercetin; C555218:7-O-pivaloxymethylquercertin; D000970:Antineoplastic Agents; D003470:Culture Media; D011355:Prodrugs; D011794:Quercetin