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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 [Bioorg Med Chem Lett] 2016 Jul 15; Vol. 26 (14), pp. 3226-3231. Date of Electronic Publication: 2016 May 24. - Publication Year :
- 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 1.71-3.06μM 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.<br /> (Copyright © 2016 Elsevier Ltd. All rights reserved.)
- Subjects :
- Antineoplastic Agents chemical synthesis
Antineoplastic Agents chemistry
Apoptosis drug effects
Cell Cycle Checkpoints drug effects
Cell Line, Tumor
Cell Proliferation drug effects
Dose-Response Relationship, Drug
Drug Screening Assays, Antitumor
Humans
Male
Molecular Structure
Prostatic Neoplasms pathology
Silymarin chemical synthesis
Silymarin chemistry
Structure-Activity Relationship
Antineoplastic Agents pharmacology
Prostatic Neoplasms drug therapy
Silymarin pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 1464-3405
- Volume :
- 26
- Issue :
- 14
- Database :
- MEDLINE
- Journal :
- Bioorganic & medicinal chemistry letters
- Publication Type :
- Academic Journal
- Accession number :
- 27261177
- Full Text :
- https://doi.org/10.1016/j.bmcl.2016.05.069