As part of our ongoing project to search for natural product-based antiandrogens, nine derivatives of 2,3-dehydrosilybin have been synthesized for the evaluation of its antiproliferative activity in an androgen receptor-positive prostate cancer cell model. Specifically, 3,5,7,20- O-tetramethyl-2,3-dehydrosilybin was synthesized through two approaches, and eight 23- O-substituted-3,5,7,20- O-tetramethyl-2,3-dehydrosilybins were achieved from 3,5,7,20- O-tetramethyl-2,3-dehydrosilybin. The antiproliferative potency of 3,5,7,20- O-tetramethyl-2,3-dehydrosilybin and its eight derivatives were assessed in an androgen receptor (AR)-positive LNCaP prostate cancer cell line, as well as in two AR-negative (PC-3 and DU145) prostate cancer cell models as a comparison. Our WST cell proliferation assay data indicate 3,5,7,20- O-tetramethyl-2,3-dehydrosilybin and most of its 23- O-substituents can selectively inhibit AR-positive LNCaP prostate cancer cell proliferation. Our data suggest that 3,5,7,20- O-tetramethyl-2,3-dehydrosilibins could serve as a natural product-based scaffold for new antiandrogens for lethal castration-resistant prostate cancer.
23-O-Substituted-2,3-Dehydrosilybins Selectively Suppress Androgen Receptor-Positive LNCaP Prostate Cancer Cell Proliferation