School of Pharmacy & Pharmaceutical Sciences, Cardiff University, Wales CF10 3NB, UK.
Molecules. 2020 Dec 24;26(1):56. doi: 10.3390/molecules26010056.
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 -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 () was the most active compound with IC = 6.59-10.86 µM. Molecular modeling offers a plausible explanation of the higher activity of the sulfide analogues compared to their sulfone counterparts.
雄激素受体（AR）是治疗前列腺癌（PC）的关键靶点，即使疾病进展为雄激素非依赖性或去势抵抗性形式。在这项研究中，制备了一系列 15 种比卡鲁胺类似物（硫化物、去羟基、砜和乙酰化），并评估了它们对四种不同的人前列腺癌细胞系（22Rv1、DU-145、LNCaP 和 VCap）的增殖活性。比卡鲁胺和恩扎鲁胺被用作阳性对照。其中 7 种化合物在四种 PC 细胞系中表现出显著增强的抗癌活性。去羟基类似物（）是最具活性的化合物，IC = 6.59-10.86µM。分子建模提供了一个合理的解释，说明硫化物类似物比砜类似物具有更高的活性。
