Design, synthesis and anticancer activity of superoxide anion-releasing beta-galactoside prodrugs
10.11665/j.issn.1000-5048.2024041401
- VernacularTitle:能释放超氧阴离子的β-半乳糖苷前药的设计、合成及抗肿瘤活性
- Author:
Jiaxuan LIU
1
,
2
,
3
;
Xueyan YAO
;
Yunying TAN
;
Jing HU
;
Junjie FU
;
Jian YIN
Author Information
1. 江南大学生物工程学院糖化学与生物技术教育部重点实验室, 无锡 214122
2. 江南大学无锡医学院, 无锡 214122
3. 江南大学生命科学与健康工程学院, 无锡 214122
- Publication Type:Journal Article
- Keywords:
superoxide anion;
β-galactoside prodrugs;
anticancer drugs
- From:
Journal of China Pharmaceutical University
2025;56(3):295-304
- CountryChina
- Language:Chinese
-
Abstract:
Four novel β-galactoside prodrugs were designed and synthesized from anthraquinones HAQ-OH and AQ-OH in an attempt to use the prodrugs to selectively release superoxide anion (O2−) in cancer cells and to achieve selected anticancer activity by utilizing the Warburg effect and the elevated level of β-galactosidase in certain cancer cells. Cellular assays showed that the prodrugs Gal-HAQ and Gal-AQ selectively inhibited the proliferation and induced apoptosis of ovarian cancer OVCAR-3 cells overexpressing β-galactosidase. Using O2− fluorescent probe, it was found that in OVCAR-3 cells Gal-HAQ and Gal-AQ could time-dependently release O2−, which was essential for their anticancer activity. Furthermore, it was found that Gal-HAQ and Gal-AQ were effective senolytics toward senescent cells overexpressing β-galactosidase without affecting the viability of corresponding non-senescent cells, further confirming the β-galactosidase-dependent cytotoxicity of the prodrugs. In conclusion, Gal-HAQ and Gal-AQ, which release O2− in response to β-galactosidase, are expected to serve as candidate prodrugs targeting cancer cells.
