Genistein is a bioactive isoflavone derived from soybeans. The tie-in between the intake of genistein
and the decreased incidence of some solid tumors (including prostate cancer) has been demonstrated by
epidemiological studies. The potential of genistein in treating prostate cancer has also been displayed by in vitro
cell-based and in vivo animal experiments. Genistein has entered clinical trials for both chemoprevention and
potential treatment of prostate cancer. Even though the low oral bioavailability has presented the major challenges
to genistein’s further clinical development, chemical modulation of genistein holds the promise to generate
potential anti-prostate cancer agents with enhanced potency and/or better pharmacokinetic profiles than genistein.
As part of our ongoing project to develop natural products-based anti-prostate cancer agents, the current study was
undertaken to synthesize eight genistein analogues for cytotoxic evaluation in three prostate cancer cell lines (PC-3, DU-145, LNCaP;
both androgen-sensitive and androgen-refractory cell lines), as well as one aggressive cervical cancer cell line (HeLa). Eight genistein
analogues have been successfully synthesized with Suzuki-Miyaura coupling reaction as a key step. Their in vitro anti-cancer potential
was evaluated by trypan blue exclusion assay and WST-1 cell proliferation assay against a panel of four human cancer cell lines. The
acquired data suggest i) that the C-5 and C-7 hydroxyl groups in genistein are very important for the cytotoxicity and anti-proliferative
activity; and ii) that 1-alkyl-1H-pyrazol-4-yl and pyridine-3-yl might act as good bioisosteres for the 4'-hydroxyphenyl moiety in
Keywords: Cytotoxicity, genistein analogue, prostate cancer, structure-activity relationship, Suzuki-Miyaura coupling reaction.
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