Synthesis and evaluation of novel thiazole-based derivatives as selective inhibitors of DNA-binding domain of the androgen receptor

Abstract

A series of thiazole-based inhibitors selectively targeting DNA-binding domain of the androgen receptor (AR) were synthesized, evaluated and the SAR data were summarized. We identified a novel compound SKLB-C2807 that effectively inhibited the human prostate cancer cell line LNCaP/AR with the IC₅₀ value of 0.38 μM without significant antiproliferative effects on other cell lines PC-3 (AR-negative), SW620, MCF-7 (ER-positive) and L-O2 (non-cancerous). This compound also considerably decreased the expression of prostate-specific antigen (PSA). Its binding mode to the AR-DBD was studied. These efforts lay the foundation for developing the next generation of anti-androgens.

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1.A series of new thiazole-based derivatives were synthesized and evaluated.

2.SKLB-C2807 effectively inhibits the LNCaP/AR and decreases the expression of prostate-specific antigen.

3.SARs and binding mode to AR-DBD studies were discussed in detail.

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