In vitro solubility, stability and permeability of novel quercetin–amino acid conjugates

Kim, Mi Kyoung; Park, Kwang‐Su; Yeo, Woon‐Seok; Choo, Hyunah; Chong, Youhoon

doi:10.1016/j.bmc.2008.12.043

Cited by 113 publications

(72 citation statements)

References 37 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Quercetin-Gly-tBu was synthesized according to Kim et al [27], with some modifications. In a 100-ml round-bottom flask (RBF), H-Gly-OtBu-HCl (1 g, 6 mmol) and bis(4-nitrophenyl) carbonate (2 g, 6.6 mmol) were dissolved in 30 ml of dry THF and 15 ml of DMF with stirring.…”

Section: Methodsmentioning

confidence: 99%

Mechanistically elucidating the in vitro safety and efficacy of a novel doxorubicin derivative

Alrushaid

Zhao

Sayre

et al. 2017

Drug Deliv. and Transl. Res.

View full text Add to dashboard Cite

Doxorubicin is an effective anticancer drug; however, it is cardiotoxic and has poor oral bioavazilability. Quercetin is a plant-based flavonoid with inhibitory effects on P-glycoprotein (P-gp) and CYP3A4 and also antioxidant properties. To mitigate these therapeutic barriers, DoxQ, a novel derivative of doxorubicin, was synthesized by conjugating quercetin to doxorubicin. The purpose of this study is to mechanistically elucidate the in vitro safety and efficacy of DoxQ. Drug release in vitro and cellular uptake by multidrug-resistant canine kidney (MDCK-MDR) cells were quantified by HPLC. Antioxidant activity, CYP3A4 inhibition, and P-gp inhibitory effects were examined using commercial assay kits. Drug potency was assessed utilizing triple-negative murine breast cancer cells, and cardiotoxicity was assessed utilizing adult rat and human cardiomyocytes (RL-14). Levels of reactive oxygen species and gene expression of cardiotoxicity markers, oxidative stress markers, and CYP1B1 were determined in RL-14. DoxQ was less cytotoxic to both rat and human cardiomyocytes and retained anticancer activity. Levels of ROS and markers of oxidative stress demonstrate lower oxidative damage induced by DoxQ compared to doxorubicin. DoxQ also inhibited the expression and catalytic activity of CYP1B1. Additionally, DoxQ inhibited CYP3A4 and demonstrated higher cellular uptake by MDCK-MDR cells than doxorubicin. DoxQ provides a novel therapeutic approach to mitigate the cardiotoxicity and poor oral bioavailability of doxorubicin. The cardioprotective mechanism of DoxQ likely involves scavenging ROS and CYP1B1 inhibition, while the mechanism of improving the poor oral bioavailability of doxorubicin is likely related to inhibiting CYP3A4 and P-gp.

show abstract

Section: Methodsmentioning

confidence: 99%

Mechanistically elucidating the in vitro safety and efficacy of a novel doxorubicin derivative

Alrushaid

Zhao

Sayre

et al. 2017

Drug Deliv. and Transl. Res.

View full text Add to dashboard Cite

show abstract

“…The stability of modified polyphenols in plasma has been examined. The quercetin-amino acid conjugates were synthesized and their stability estimated against PBS (Kim et al, 2009b). Several amino acid conjugates were stable in PBS buffer (t 1/2 417 h), and there was strong resistance against hydrolases compared to quercetin.…”

Section: Discussionmentioning

confidence: 99%

Synthesis and biological evaluation of a novel baicalein glycoside as an anti-inflammatory agent

Kim¹,

Park²,

Park³

et al. 2014

European Journal of Pharmacology

View full text Add to dashboard Cite

“…Moreover, methods for the preparation of quercetin metabolites have also been developed [5], [6]. The quercetin derivatives synthesized to date include, for instance, esters of quercetin and of various aliphatic [7], [8] and aromatic carboxylic acids [9], [10], [11], quercetin-amino acid conjugates with amino acids attached to quercetin via a carbamate linkage [12], esters of sulfuric acid (i.e. quercetin sulfates) [13], [14], glycosides [15], glucuronides [5], methyl ethers [16], etc.…”

Section: Introductionmentioning

confidence: 99%

Semisynthetic flavonoid 7-O-galloylquercetin activates Nrf2 and induces Nrf2-dependent gene expression in RAW264.7 and Hepa1c1c7 cells

Roubalová¹,

Biedermann

Papoušková

et al. 2016

Chemico-Biological Interactions

View full text Add to dashboard Cite

The natural flavonoid quercetin is known to activate the transcription factor Nrf2, which regulates the expression of cytoprotective enzymes such as heme oxygenase-1 (HO-1) and NAD(P)H:quinone oxidoreductase 1 (NQO1). In this study, a novel semisynthetic flavonoid 7-O-galloylquercetin (or quercetin-7-gallate, 3) was prepared by direct galloylation of quercetin, and its effect on the Nrf2 pathway was examined. A luciferase reporter assay showed that 7-O-galloylquercetin, like quercetin, significantly activated transcription via the antioxidant response element in a stably transfected human AREc32 reporter cell line. In addition, 7-O-galloylquercetin caused the accumulation of Nrf2 and induced the expression of HO-1 at both the mRNA and protein levels in murine macrophage RAW264.7 cells. The induction of HO-1 by 7-O-galloylquercetin was significantly suppressed by N-acetyl-l-cysteine and SB203580, indicating the involvement of reactive oxygen species and p38 mitogen-activated protein kinase activity, respectively. HPLC/MS analyses also showed that 7-O-galloylquercetin was not degalloylated to quercetin, but it was conjugated with glucuronic acid and/or methylated in RAW264.7 cells. Furthermore, 7-O-galloylquercetin was found to increase the protein levels of Nrf2 and HO-1, and also the activity of NQO1 in murine hepatoma Hepa1c1c7 cells. Taken together, we conclude that 7-O-galloylquercetin increases Nrf2 activity and induces Nrf2-dependent gene expression in RAW264.7 and Hepa1c1c7 cells.

show abstract

In vitro solubility, stability and permeability of novel quercetin–amino acid conjugates

Cited by 113 publications

References 37 publications

Mechanistically elucidating the in vitro safety and efficacy of a novel doxorubicin derivative

Mechanistically elucidating the in vitro safety and efficacy of a novel doxorubicin derivative

Synthesis and biological evaluation of a novel baicalein glycoside as an anti-inflammatory agent

Semisynthetic flavonoid 7-O-galloylquercetin activates Nrf2 and induces Nrf2-dependent gene expression in RAW264.7 and Hepa1c1c7 cells

Contact Info

Product

Resources

About