Cho, Suh Young Kim, Mi Kyoung Park, Kwang-su Choo, Hyunah Chong, Youhoon 2024-01-20T12:32:48Z 2024-01-20T12:32:48Z 2021-09-05 2013-04-01 0968-0896 https://pubs.kist.re.kr/handle/201004/128165 In the course of our ongoing efforts to develop novel quercetin conjugates with enhanced stability profiles, we introduced an isopropyloxycarbonylmethoxy (POC) group to 7-OH and/or 3-OH of quercetin and prepared three novel quercetin conjugates. The quercetin-POC conjugates were stable up to 96 h in PBS but slowly hydrolyzed with half-lives of 1-54 h in cell-free culture medium, which is reminiscent of the stability profiles of the previously reported quercetin-POM (pivaloxymethyl) conjugates. However, the quercetin-POC conjugates were more susceptible to passive transport, intracellular hydrolysis, and metabolism in breast cancer (MCF-7) cell line compared with their POM congeners to result in low concentration of quercetin in this cell line and thereby low antiproliferative effect. In contrast, upon incubation with colorectal carcinoma HCT116 cells, the quercetin-POC conjugates were shown to undergo slow hydrolysis and metabolism to maintain concentrations of the active quercetin species high enough to exert enhanced cytotoxicity. Taken together, the quercetin-POC conjugates synthesized in this study exhibited cell type-specific stability as well as bioactivity profiles, which warrants further investigation into the underlying mechanisms and therapeutic potential. (C) 2013 Elsevier Ltd. All rights reserved. English PERGAMON-ELSEVIER SCIENCE LTD PHASE PHARMACOKINETICS DERIVATIVES TRIAL ASSAY Quercetin-POC conjugates: Differential stability and bioactivity profiles between breast cancer (MCF-7) and colorectal carcinoma (HCT116) cell lines Article 10.1016/j.bmc.2013.01.057 1 BIOORGANIC & MEDICINAL CHEMISTRY, v.21, no.7, pp.1671 - 1679 BIOORGANIC & MEDICINAL CHEMISTRY 21 7 1671 1679 scie scopus 000316770300007 2-s2.0-84875228787 Biochemistry & Molecular Biology Chemistry, Medicinal Chemistry, Organic Biochemistry & Molecular Biology Pharmacology & Pharmacy Chemistry Article PHASE PHARMACOKINETICS DERIVATIVES TRIAL ASSAY Quercetin Isopropyloxycarbonylmethoxy (POC) Conjugate Stability Metabolism