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Synthesis and Biological Evaluation of Bicalutamide Analogues for the Potential Treatment of Prostate Cancer.

ABSTRACT: The androgen receptor (AR) is a pivotal target for the treatment of prostate cancer (PC) even when the disease progresses toward androgen-independent or castration-resistant forms. In this study, a series of 15 bicalutamide analogues (sulfide, deshydroxy, sulfone, and O-acetylated) were prepared and their antiproliferative activity evaluated against four different human prostate cancer cell lines (22Rv1, DU-145, LNCaP, and VCap). Bicalutamide and enzalutamide were used as positive controls. Seven of these compounds displayed remarkable enhancement in anticancer activity across the four PC cell lines. The deshydroxy analogue (16) was the most active compound with IC₅₀ = 6.59-10.86 µM. Molecular modeling offers a plausible explanation of the higher activity of the sulfide analogues compared to their sulfone counterparts.

SUBMITTER: Kandil SB

PROVIDER: S-EPMC7795644 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature

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Synthesis and Biological Evaluation of Bicalutamide Analogues for the Potential Treatment of Prostate Cancer.

Kandil Sahar B SB McGuigan Christopher C Westwell Andrew D AD

Molecules (Basel, Switzerland) 20201224 1

The androgen receptor (AR) is a pivotal target for the treatment of prostate cancer (PC) even when the disease progresses toward androgen-independent or castration-resistant forms. In this study, a series of 15 bicalutamide analogues (sulfide, deshydroxy, sulfone, and <i>O</i>-acetylated) were prepared and their antiproliferative activity evaluated against four different human prostate cancer cell lines (22Rv1, DU-145, LNCaP, and VCap). Bicalutamide and enzalutamide were used as positive control ...[more]

PMID: 33374450

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