3-O-Alkyl-2,3-dehydrosilibinins: Two synthetic approaches and in vitro effects toward prostate cancer cells.
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.
Department of Chemistry, California State University, Fresno, 2555 E. San Ramon Avenue, M/S SB70, Fresno, CA 93740, USA.
Sheng
S
Zhang
Department of Chemistry, California State University, Fresno, 2555 E. San Ramon Avenue, M/S SB70, Fresno, CA 93740, USA.
Bao
B
Vue
Department of Chemistry, California State University, Fresno, 2555 E. San Ramon Avenue, M/S SB70, Fresno, CA 93740, USA.
Michael
M
Huang
Department of Chemistry, California State University, Fresno, 2555 E. San Ramon Avenue, M/S SB70, Fresno, CA 93740, USA.
Xiaojie
X
Zhang
Department of Chemistry, California State University, Fresno, 2555 E. San Ramon Avenue, M/S SB70, Fresno, CA 93740, USA.
Timmy
T
Lee
Department of Chemistry, California State University, Fresno, 2555 E. San Ramon Avenue, M/S SB70, Fresno, CA 93740, USA.
Guanglin
G
Chen
RCMI Cancer Research Center, Xavier University of Louisiana, 1 Drexel Drive, New Orleans, LA 70125, USA.
Qiang
Q
Zhang
RCMI Cancer Research Center, Xavier University of Louisiana, 1 Drexel Drive, New Orleans, LA 70125, USA.
Shilong
S
Zheng
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.
Guangdi
G
Wang
Department of Chemistry, California State University, Fresno, 2555 E. San Ramon Avenue, M/S SB70, Fresno, CA 93740, USA.
Qiao-Hong
QH
Chen
D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D059447:Cell Cycle Checkpoints / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D008297:Male; D015394:Molecular Structure; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000473:pathology; D012838:Silymarin / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
D000970:Antineoplastic Agents; D012838:Silymarin; C515097:dehydrosilybin
Cell apoptosis; Cell cycle regulation; Cell proliferation; Prostate cancer; Silibinin