2. Academic Validation
  3. 3-O-Alkyl-2,3-dehydrosilibinins: Two synthetic approaches and in vitro effects toward prostate cancer cells

3-O-Alkyl-2,3-dehydrosilibinins: Two synthetic approaches and in vitro effects toward prostate cancer cells

  • Bioorg Med Chem Lett. 2016 Jul 15;26(14):3226-3231. doi: 10.1016/j.bmcl.2016.05.069.
Sheng Zhang 1,  Bao Vue 1,  Michael Huang 1,  Xiaojie Zhang 1,  Timmy Lee 1,  Guanglin Chen 1,  Qiang Zhang 2,  Shilong Zheng 2,  Guangdi Wang 3,  Qiao-Hong Chen 1
Affiliations

Affiliations

  • 1 Department of Chemistry, California State University, Fresno, 2555 E. San Ramon Avenue, M/S SB70, Fresno, CA 93740, USA.
  • 2 RCMI Cancer Research Center, Xavier University of Louisiana, 1 Drexel Drive, New Orleans, LA 70125, USA.
  • 3 RCMI Cancer Research Center, Xavier University of Louisiana, 1 Drexel Drive, New Orleans, LA 70125, USA; Department of Chemistry, Xavier University of Louisiana, 1 Drexel Drive, New Orleans, LA 70125, USA.
PMID: 27261177 DOI: 10.1016/j.bmcl.2016.05.069
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 1.71-3.06μM 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 G0/G1 phase, but not by activating PC-3 cell Apoptosis.

Keywords

Cell apoptosis; Cell cycle regulation; Cell proliferation; Prostate cancer; Silibinin.

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