喹啉酮
细胞凋亡
达皮
赫拉
细胞毒性
膜联蛋白
细胞周期
化学
流式细胞术
活性氧
免疫印迹
细胞生物学
分子生物学
线粒体
生物
生物化学
细胞
体外
立体化学
基因
作者
Kesari Lakshmi Manasa,Mohd Aslam Saifi,Yellaiah Tangella,Chandraiah Godugu,Mallika Alvala
出处
期刊:Anti-cancer Agents in Medicinal Chemistry
[Bentham Science]
日期:2020-01-23
卷期号:19 (16): 1935-1948
被引量:8
标识
DOI:10.2174/1871520619666190906162537
摘要
Background: The synthesis of novel heterocyclic scaffolds with amide functionality is a key research area due to their plethora of medicinal applications. The present study aims to explore the synthesis of new cinnamido linked quinazolinone congeners and their potential as anticancer agents. Methods: Cytotoxicity evaluation, Cell cycle analysis, JC-1 staining, ROS, Annexin V assays, AO/EB, DAPI nuclear staining, Colony-forming assay and Western blot analysis. Results: Among the synthesized compounds, 5eb and 5fc have shown promising cytotoxic activity with an IC50 value of 3.89±1.01µM and 4.05±0.62µM against HeLa cell lines. The flow-cytometry analysis demonstrated that the compound 5eb arrested the sub-G1 phase of the cell cycle and induced apoptosis. Furthermore, the compound 5eb triggered the collapse of mitochondrial membrane potential (ΔΨm), which was assessed by JC-1 staining and also induced the generation of Reactive Oxygen Species. An increase in the expression of proapoptotic proteins such as Bax, p53, cleaved PARP and cleaved caspase-3 by 5eb confirmed the activation of the mitochondrial-dependent intrinsic apoptosis pathway. Conclusion: Our results suggest that compound 5eb and 5fc of cinnamido linked quinazolinone derivatives could serve as potential leads in the development of novel chemotherapeutic agents.
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