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5- or/and 20-O-alkyl-2,3-dehydrosilybins: Synthesis and biological profiles on prostate cancer cell models
- Source :
- Bioorganic & Medicinal Chemistry. 25:4845-4854
- Publication Year :
- 2017
- Publisher :
- Elsevier BV, 2017.
-
Abstract
- To investigate the effects of alkylation at 5-OH and 20-OH of 2,3-dehydrosilybin on prostate cancer cell proliferation, the synthetic approaches to 5- or/and 20-O-alkyl-2,3-dehydrosilybins, through a multi-step sequence from commercially available silybin, have been successfully developed. The first three reactions in the syntheses were completed through a one-pot procedure by managing anaerobic and aerobic conditions. With these synthetic methods in hand, twenty-one 2,3-dehydrosilybins, including seven 20-O-alkyl, seven 5,20-O-dialkyl, and seven 5-O-alkyl-2,3-dehydrosilybins, have been achieved for the evaluation of their biological profiles. Our WST-1 cell proliferation assay data indicate that nineteen out of the twenty-one 2,3-dehydrosilybins possess significantly improved antiproliferative potency as compared with silybin toward both androgen-sensitive (LNCaP) and androgen-insensitive prostate cancer cell lines (PC-3 and DU145). 5-O-Alkyl-2,3-dehydrosilybins were identified as the optimal subgroup that can consistently inhibit cell proliferation in three prostate cancer cell models with all IC50 values lower than 8 μM. Our flow cytometry-based assays also demonstrate that 5-O-heptyl-2,3-dehydrosilybin effectively arrests the cell cycle in the G0/G1 phase and activates PC-3 cell apoptosis.
- Subjects :
- Male
0301 basic medicine
medicine.medical_specialty
Clinical Biochemistry
Pharmaceutical Science
Antineoplastic Agents
Apoptosis
Biochemistry
Article
Flow cytometry
Structure-Activity Relationship
03 medical and health sciences
Prostate cancer
0302 clinical medicine
DU145
Cell Line, Tumor
Internal medicine
Drug Discovery
LNCaP
medicine
Humans
Potency
Molecular Biology
Cell Proliferation
medicine.diagnostic_test
Cell growth
Chemistry
Organic Chemistry
Prostatic Neoplasms
Cell cycle
medicine.disease
G1 Phase Cell Cycle Checkpoints
030104 developmental biology
Endocrinology
030220 oncology & carcinogenesis
Cancer research
Molecular Medicine
Drug Screening Assays, Antitumor
Silymarin
Subjects
Details
- ISSN :
- 09680896
- Volume :
- 25
- Database :
- OpenAIRE
- Journal :
- Bioorganic & Medicinal Chemistry
- Accession number :
- edsair.doi.dedup.....e100ee0db891eda17ac383d5c50ecb93