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3- O -Alkyl-2,3-dehydrosilibinins: Two synthetic approaches and in vitro effects toward prostate cancer cells
- Source :
- Bioorganic & Medicinal Chemistry Letters. 26:3226-3231
- Publication Year :
- 2016
- Publisher :
- Elsevier BV, 2016.
-
Abstract
- Eight 3-O-alkyl-2,3-dehydrosilibinins have been synthesized from commercially available silibinin through two synthetic approaches. A one-pot reaction, starting with aerobic oxidation of silibinin followed by direct alkylation of the phenolic hydroxyl group in the subsequent 2,3-dehydrosilibinin, furnishes the desired derivatives in 11–16% yields. The three-step procedure employing benzyl ether to protect 7-OH in silibinin generates the desired derivatives in 30–46% overall yields. The antiproliferative activity of the 2,3-dehydrosilibinin derivatives against both androgen-sensitive and androgen-insensitive prostate cancer cells have been assessed using a WST-1 cell proliferation assay. All derivatives exhibited greater antiproliferative potency than silibinin, with 2,3-dehydrosilibinins each possessing a three- to five-carbon linear alkyl group to 3-OH (IC50 values in a range of 1.71 to 3.06 μM against PC-3 and LNCaP cells) as the optimal derivatives. The optimal potency was reached with three- to five-carbon alkyl groups. Our findings suggest that 3-O-propyl-2,3-dehydrosilibinin effectively inhibits the growth of PC-3 prostate cancer cells by arresting cell cycle in the G0/G1 phase, but not by activating PC-3 cell apoptosis.
- Subjects :
- Male
0301 basic medicine
Stereochemistry
Clinical Biochemistry
Pharmaceutical Science
Silibinin
Antineoplastic Agents
Apoptosis
Alkylation
Biochemistry
Article
Structure-Activity Relationship
03 medical and health sciences
chemistry.chemical_compound
0302 clinical medicine
Cell Line, Tumor
Drug Discovery
LNCaP
Humans
Structure–activity relationship
Molecular Biology
Alkyl
Cell Proliferation
chemistry.chemical_classification
Dose-Response Relationship, Drug
Molecular Structure
Cell growth
Chemistry
Organic Chemistry
Prostatic Neoplasms
Cell Cycle Checkpoints
Cell cycle
030104 developmental biology
030220 oncology & carcinogenesis
Molecular Medicine
Drug Screening Assays, Antitumor
Silymarin
Subjects
Details
- ISSN :
- 0960894X
- Volume :
- 26
- Database :
- OpenAIRE
- Journal :
- Bioorganic & Medicinal Chemistry Letters
- Accession number :
- edsair.doi.dedup.....688ae8201f0fb63135a7ff5b20244874