3-O-Alkyl-2, 3-dehydrosilibinins: Two synthetic approaches and in vitro effects toward prostate cancer cells. Issue 14 (15th July 2016) - Zhang, Sheng
Graphical abstract: Abstract: Eight 3- O -alkyl-2, 3-dehydrosilibinins have been synthesized from commercially available silibinin through two synthetic approaches. A one-pot reaction, starting with aerobic oxidation of silibinin followed by direct alkylation of the phenolic hydroxyl group in the subsequent 2, 3-dehydrosilibinin, furnishes the desired derivatives in 11–16% yields. The three-step procedure employing benzyl ether to protect 7-OH in silibinin generates the desired derivatives in 30–46% overall yields. The antiproliferative activity of the 2, 3-dehydrosilibinin derivatives against both androgen-sensitive and androgen-insensitive prostate cancer cells have been assessed using a WST-1 cell proliferation assay. All derivatives exhibited greater antiproliferative potency than silibinin, with 2, 3-dehydrosilibinins each possessing a three- to five-carbon linear alkyl group to 3-OH (IC50 values in a range of 1.71–3.06 μM against PC-3 and LNCaP cells) as the optimal derivatives. The optimal potency was reached with three- to five-carbon alkyl groups. Our findings suggest that 3- O -propyl-2, 3-dehydrosilibinin effectively inhibits the growth of PC-3 prostate cancer cells by arresting cell cycle in the G 0 / G 1 phase, but not by activating PC-3 cell apoptosis.