title: Biomimetic syntheses and antiproliferative activities of racemic, natural (-), and unnnatural (+) glyceollin I.
abstract: A 14-step biomimetic synthetic route to glyceollin I (1.5% overall yield) was developed and deployed to produce the natural enantiomeric form in soy, its unnatural stereoisomer, and a racemic mixture. Enantiomeric excess was assessed by asymmetric NMR shift reagents and chiral HPLC. Antiproliferative effects were measured in human breast, ovarian, and prostate cancer cell lines, with all three chiral forms exhibiting growth inhibition (GI) in the low to mid μM range for all cells. The natural enantiomer, and in some cases the racemate, gave significantly greater GI than the unnatural stereoisomer for estrogen receptor positive (ER(+)) versus ER(-) breast/ovarian cell lines as well as for androgen receptor positive (AR(+)) versus AR(-) prostate cancer cells. Surprisingly, differences between ER(+) and ER(-) cell lines were not altered by media estrogen conditions. These results suggest the antiproliferative mechanism of glyceollin I stereoisomers may be more complicated than strictly ER interactions.
authors.affiliation: University of Findlay, College of Pharmacy, Findlay, Ohio 45840, United States.
authors.forename: Rahul S
authors.initials: RS
authors.lastname: Khupse
authors.forename: Jeffrey G
authors.initials: JG
authors.lastname: Sarver
authors.forename: Jill A
authors.initials: JA
authors.lastname: Trendel
authors.forename: Nicole R
authors.initials: NR
authors.lastname: Bearss
authors.forename: Michael D
authors.initials: MD
authors.lastname: Reese
authors.forename: Thomas E
authors.initials: TE
authors.lastname: Wiese
authors.forename: Stephen M
authors.initials: SM
authors.lastname: Boue
authors.forename: Matthew E
authors.initials: ME
authors.lastname: Burow
authors.forename: Thomas E
authors.initials: TE
authors.lastname: Cleveland
authors.forename: Deepak
authors.initials: D
authors.lastname: Bhatnagar
authors.forename: Paul W
authors.initials: PW
authors.lastname: Erhardt
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D032701:Biomimetics; D001943:Breast Neoplasms / Q000188:drug therapy; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D004354:Drug Screening Assays, Antitumor / Q000379:methods; D005260:Female; D006801:Humans; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D008297:Male; D008956:Models, Chemical; D010051:Ovarian Neoplasms / Q000188:drug therapy; D011471:Prostatic Neoplasms / Q000188:drug therapy; D036343:Pterocarpans / Q000737:chemistry*; D011960:Receptors, Estrogen / Q000378:metabolism; D013237:Stereoisomerism
chemical_list: D000970:Antineoplastic Agents; D036343:Pterocarpans; D011960:Receptors, Estrogen; C017343:glyceollin