Title
O-Aminoalkyl-O-trimethyl-2,3-dehydrosilybins: Synthesis and In Vitro Effects Towards Prostate Cancer Cells.
Funding Source
Xavier University of Louisiana, Agenzia Spaziale Italiana, California State University, National Institutes of Health
Grant Number
2G12MD007595
Department
Department of Chemistry
Document Type
Article
Publication Date
11-29-2019
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 IC 50 values in the range of 1.40–3.06 µM, 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 G 0 /G 1 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.
Recommended Citation
Vue, B.; Zhang, S.; Vignau, A.; Chen, G.; Zhang, X.; Diaz, W.; Zhang, Q; Zheng, Shilong; Wang, Guangdi; and Chen, Q. H., "O-Aminoalkyl-O-trimethyl-2,3-dehydrosilybins: Synthesis and In Vitro Effects Towards Prostate Cancer Cells." (2019). Faculty and Staff Publications. 121.
https://digitalcommons.xula.edu/fac_pub/121
Comments
DOI: 10.3390/molecules23123142
PubMed ID: 30501133
Funding text
Funding: This work was financially supported by California State University (CSU)-Fresno. HRMS were supported by the NIH RCMI program at Xavier University of Louisiana through Grant [2G12MD007595] (G. Wang). We are also grateful to (i) the ASI at CSU-Fresno for a Graduate Research Grant (to S. Zhang), (ii) the Graduate Net Initiative at CSU-Fresno for 2015–2016 Graduate Research Fellowships (to S. Zhang and X. Zhang), and (iii) the Undergraduate Research Grant program at CSU-Fresno for the funding (to A. Vignau and W. Diaz). We are grateful to the Henry Madden Library Open Access mini-grant program (CSU-Fresno) for an Open Access Mini-Grant.