Chemistry Department, Lomonosov Moscow State University, Leninskie Gory, Building 1/3, GSP-1, 119991 Moscow, Russia.
N.N. Blokhin Russian Cancer Research Center, 24 Kashirskoye sh., 115478 Moscow, Russia.
Molecules. 2022 Dec 12;27(24):8795. doi: 10.3390/molecules27248795.
Prostate cancer is the second most common type of cancer among men. The main method of its treatment is androgen deprivation therapy, which has a wide range of side effects. One of the solutions to this challenge is the targeted delivery of drugs to prostate cancer cells. In this study, we performed the synthesis of a novel small-molecule PSMA-targeted conjugate based on abiraterone. Cytotoxicity, the induction of intracellular reactive oxygen species, and P450-cytochrome species inhibition were investigated for this conjugate PSMA-abiraterone. The conjugate demonstrated a preferential effect on prostate tumor cells, remaining inactive at up to 100 µM in human fibroblast cells. In addition, it revealed preferential efficacy, specifically on PSMA-expressing lines with a 65% tumor growth inhibition level on 22Rv1 (PSMA+) xenografts after 14-fold oral administration of at a single dose of 500 mg/kg (7.0 g/kg total dose) was observed. This compound showed significantly reduced acute toxicity with comparable efficacy compared to .
前列腺癌是男性中第二常见的癌症类型。其主要治疗方法是雄激素剥夺疗法，但这种方法有广泛的副作用。针对这一挑战的解决方案之一是将药物靶向递送到前列腺癌细胞中。在这项研究中，我们基于阿比特龙合成了一种新型的小分子 PSMA 靶向缀合物。研究了这种 PSMA-阿比特龙缀合物的细胞毒性、细胞内活性氧诱导和 P450-细胞色素种类抑制作用。该缀合物对前列腺肿瘤细胞表现出优先作用，在高达 100 μM 的浓度下对人成纤维细胞仍保持不活跃。此外，它在 PSMA 表达系上表现出优先的疗效，在单次口服 500mg/kg（总剂量 7.0g/kg）的剂量下，22Rv1（PSMA+）异种移植的肿瘤生长抑制水平达到 65%。与 相比，该化合物的急性毒性显著降低，且疗效相当。
