Abstract Celebrex, a nonsteroidal
anti-inflammatory drug (NSAID, cyclooxygenase-2 inhibitor), was reported to induce
apoptosis in the prostate cancer cell line PC-3 at 50μM. Early research from our laboratory demonstrated that this apoptotic inducing effect was independent of its COX-2 inhibitory activity. Further investigation showed that PDK-I was a major protein targeted by celebrex in PC-3 cells to induce apoptosis. However, celebrex was very weak in inhibiting PDK-1 with IC50 of 48μM. To improve its potency, two series of analogs were designed and synthesized. In the first series of 24 compounds, the 5-position methylphenyl moiety of celebrex was replaced by various aromatic ring…
