Document Report Card

ID: ALA1772990

Journal: J Med Chem

Title: Biomimetic syntheses and antiproliferative activities of racemic, natural (-), and unnnatural (+) glyceollin I.

Authors: Khupse RS, Sarver JG, Trendel JA, Bearss NR, Reese MD, Wiese TE, Boue SM, Burow ME, Cleveland TE, Bhatnagar D, Erhardt PW.

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.

CiteXplore: 21513275

DOI: 10.1021/jm101619e