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Synthesis and Anti-Proliferative Effects of Quercetin Derivatives
- Source :
- Natural Product Communications. 10:1934578X1501001
- Publication Year :
- 2015
- Publisher :
- SAGE Publications, 2015.
-
Abstract
- Prostate cancer is the most common diagnosed invasive cancer in American men and is the second leading cause of cancer-related deaths. Although there are several therapies successful in treating early, localized stage prostate cancer, current treatment of advanced metastatic castration-resistant prostate cancer remains ineffective due to inevitable progression of resistance to first-line treatment with docetaxel. The natural product quercetin (3,3′,4′,5,7-pentahydroxyflavone), a flavonoid compound ubiquitous in dietary plants, possesses evidenced potential in treating advanced metastatic castration-resistant prostate cancer. However, its poor bioavailability and moderate potency hinder its advancement into clinical therapy. In order to engineer quercetin derivatives with improved potency and pharmacokinetic profiles for the treatment of advanced metastatic prostate cancer, we started this study with creating a small library of alkylated derivatives of quercetin for in vitro evaluation. The biological data and chemical reactivity of quercetin and its derivatives reported in literature directed us to design 3,4′,7- O-trialkylquercetins as our first batch of targets. Consequently, nine 3,4′,7- O-trialkylquercetins, together with four 3,7- O-dialkylquercetins, four 3,3′,4′,7-tetraalkylquercetins, and one 3,3′,4′- O-trialkylquercetin, were prepared by one step O-alkylation of commercially available quercetin mediated by potassium carbonate. Their structures were determined by 1D and 2D NMR data, and HRMS. Their anti-proliferative activities towards both androgen-refractory and androgen-sensitive prostate cancer cells were evaluated using WST-1 cell proliferation assay. The acquired structure-activity relationships indicate that 3,7- O-dialkylquercetins rather than 3,4′,7- O-trialkylquercetins were much more potent than quercetin towards prostate cancer cells.
- Subjects :
- Male
Flavonoid
Plant Science
Prostate cancer
chemistry.chemical_compound
Cell Line, Tumor
Drug Discovery
medicine
Humans
Potency
Cell Proliferation
Pharmacology
chemistry.chemical_classification
Natural product
Molecular Structure
Cell growth
business.industry
Prostatic Neoplasms
General Medicine
medicine.disease
Antineoplastic Agents, Phytogenic
In vitro
Complementary and alternative medicine
chemistry
Docetaxel
Cancer research
Quercetin
business
medicine.drug
Subjects
Details
- ISSN :
- 15559475 and 1934578X
- Volume :
- 10
- Database :
- OpenAIRE
- Journal :
- Natural Product Communications
- Accession number :
- edsair.doi.dedup.....4bbad2311639f1fe69ffdecda51c035a