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Silibinin derivatives as anti-prostate cancer agents: Synthesis and cell-based evaluations
- Source :
- European Journal of Medicinal Chemistry. 109:36-46
- Publication Year :
- 2016
- Publisher :
- Elsevier BV, 2016.
-
Abstract
- This study aims to systematically explore the alkylation effect of 7-OH in silibinin and 2,3-dehydrosilibinin on the antiproliferative potency toward three prostate cancer cell lines. Eight 7-O-alkylsilibinins, eight 7-O-alkyl-2,3-dehydrosilibinins, and eight 3,7-O-dialkyl-2,3-dehydrosilibinins have been synthesized from commercially available silibinin for the in vitro cell-based evaluation. The WST-1 cell proliferation assay indicates that nineteen out of twenty-four silibinin derivatives have significantly improved antiproliferative potency when compared with silibinin. 7-O-Methylsilibinin (2) and 7-O-ethylsilibinin (3) have been identified as the most potent compounds with 98- and 123-fold enhanced potency against LNCaP human androgen-dependent prostate cancer cell line. Among 2,3-dehydrosilibinin derivatives, 7-O-methyl-2,3-dehydrosilibinin (10) and 7-O-ethyl-2,3-dehydrosilibinin (11) have been identified as the optimal compounds with the highest potency towards both androgen-dependent LNCaP and androgen-independent PC-3 prostate cancer cell lines. 7-O-Ethyl-2,3-dehydrosilibinin (11) was demonstrated to arrest PC-3 cell cycle at the G0/G1 phase and to induce PC-3 cell apoptosis. The findings in this study suggest that antiproliferative potency of silibinin and 2,3-dehydrosilibinin can be appreciably enhanced through suitable chemical modifications on the phenolic hydroxyl group at C-7 and that introduction of a chemical moiety with the potential to improve bioavailability through a linker to 7-OH in silibinin and 2,3-dehydrosilibinin would be a feasible strategy for the development of silibinin derivatives as anti-prostate cancer agents.
- Subjects :
- Male
0301 basic medicine
Silibinin
Antineoplastic Agents
Apoptosis
Pharmacology
Article
03 medical and health sciences
Prostate cancer
chemistry.chemical_compound
0302 clinical medicine
Cell Line, Tumor
Drug Discovery
LNCaP
medicine
Humans
Structure–activity relationship
Potency
Cell Proliferation
Cell growth
Chemistry
Cell Cycle
Organic Chemistry
G1 Phase
Prostate
Prostatic Neoplasms
Cancer
General Medicine
Cell cycle
medicine.disease
030104 developmental biology
Silybin
030220 oncology & carcinogenesis
Silymarin
Subjects
Details
- ISSN :
- 02235234
- Volume :
- 109
- Database :
- OpenAIRE
- Journal :
- European Journal of Medicinal Chemistry
- Accession number :
- edsair.doi.dedup.....e58f6dbbffe25a03bc497065a72d51b0