2-Azetidinones: Synthesis and biological evaluation as potential anti-breast cancer agents.
作者： Ramasatyaveni Geesala , Jagadeesh Kumar Gangasani , Mahender Budde , Sridhar Balasubramanian , Jayathirtha Rao Vaidya
DOI: 10.1016/J.EJMECH.2016.08.041
关键词: Cancer research 、 Cell cycle checkpoint 、 Phosphorylation 、 Cell biology 、 Chemistry 、 Protein kinase B 、 Cyclin 、 AKT1 、 Apoptosis 、 Cyclin-dependent kinase 、 Cytotoxicity
摘要: A series of twenty-five 2-azitidinone (β-lactam) derivatives were synthesized and evaluated for anti-cancer properties against breast cancer, MCF-7 MDA-MB-231. These β-lactam depicted significant cytotoxicity in cancer cell lines but not normal human mammary epithelial cells, MEpiC. Interestingly, 2-bromo ethyl acrylonitrile (19w) exhibited - potent anti-proliferative activity with IC50, 5.79 ± 0.01 μM 6.86 ± 0.009 μM In addition, an increased expression pro-apoptotic genes (p53, Bax, Bid) as well decreased mRNA cyclins D1, E Cdk 2, 6 along cycle arrest at G1 phase was observed. 19w treatment has shown higher percentage Annexin-positive cells indicating induction apoptosis. Further, docking studies confirmed interaction between ATP-binding catalytic site AKT1. Mechanistically, dose-dependent decrease phosphorylation AKT GSK-3β kinase activity. conclusion, derivative is a potential anti-breast therapeutic candidate targeting survival pathway (AKT/GSK3β).
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