Pharmacology, Toxicology and Environmental Health Commons^™

Design And Synthesis Of Enzalutamide-Isothiocyanate Hybrid Drug As Anti-Prostate Cancer Agent, Siyu Ou

Wayne State University Theses

Isothiocyanate (ITC), such as sulforaphane (SFN), is an active metabolite of dietary glucosinolate from cruciferous vegetables. SFN-rich extracts have been recently tested in recurrent prostate cancer (PCa) patients and notably prolonged PSA doubling time without Grade 3 adverse events. One of the anti-PCa mechanisms of SFN is to inhibit HDAC6, which further triggering androgen receptor (AR) degradation. We have incorporated ITC to the chemical scaffold of enzalutamide (Enz) to create Enz-ITC hybrid molecules with an intention to intracellularly deliver ITC to AR-Hsp90-HDAC6 complex and therefore improving anti-PCa efficacy of both parental drugs. Two Enz-ITCs and one Enz-ITC N-acetyl cysteine (NAC) …