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O-Aminoalkyl-O-Trimethyl-2,3-Dehydrosilybins: Synthesis and In Vitro Effects Towards Prostate Cancer Cells
- Source :
- Molecules, Molecules, Vol 23, Iss 12, p 3142 (2018), Volume 23, Issue 12
- Publication Year :
- 2018
- Publisher :
- MDPI AG, 2018.
-
Abstract
- As part of our ongoing silybin project, this study aims to introduce a basic nitrogen-containing group to 7-OH of 3,5,20-O-trimethyl-2,3-dehydrosilybin or 3-OH of 5,7,20-O-trimethyl-2,3-dehydrosilybin via an appropriate linker for in vitro evaluation as potential anti-prostate cancer agents. The synthetic approaches to 7-O-substituted-3,5,20-O-trimethyl-2,3-dehydrosilybins through a five-step procedure and to 3-O-substituted-5,7,20-O-trimethyl-2,3- dehydrosilybins via a four-step transformation have been developed. Thirty-two nitrogen-containing derivatives of silybin have been achieved through these synthetic methods for the evaluation of their antiproliferative activities towards both androgen-sensitive (LNCaP) and androgen-insensitive prostate cancer cell lines (PC-3 and DU145) using the WST-1 cell proliferation assay. These derivatives exhibited greater in vitro antiproliferative potency than silibinin. Among them, 11, 29, 31, 37, and 40 were identified as five optimal derivatives with IC50 values in the range of 1.40&ndash<br />3.06 &micro<br />M, representing a 17- to 52-fold improvement in potency compared to silibinin. All these five optimal derivatives can arrest the PC-3 cell cycle in the G0/G1 phase and promote PC-3 cell apoptosis. Derivatives 11, 37, and 40 are more effective than 29 and 31 in activating PC-3 cell apoptosis.
- Subjects :
- 2,3-dehydrosilybin
Pharmaceutical Science
Silibinin
01 natural sciences
Article
silybin
Analytical Chemistry
lcsh:QD241-441
03 medical and health sciences
chemistry.chemical_compound
0302 clinical medicine
lcsh:Organic chemistry
DU145
Drug Discovery
LNCaP
medicine
Physical and Theoretical Chemistry
cell apoptosis
010405 organic chemistry
Cell growth
Chemistry
medicinal_chemistry
Organic Chemistry
Cancer
Cell cycle
prostate cancer
medicine.disease
In vitro
0104 chemical sciences
3. Good health
cell proliferation
Chemistry (miscellaneous)
Apoptosis
030220 oncology & carcinogenesis
Cancer research
Molecular Medicine
Subjects
Details
- ISSN :
- 14203049
- Volume :
- 23
- Database :
- OpenAIRE
- Journal :
- Molecules
- Accession number :
- edsair.doi.dedup.....7fc18a76f568ee0e3b4ec43a7e949de6