新型苯乙烯基咪唑并[1,2-a]吡啶类化合物的设计、合成、体外细胞毒性活性评价及诱导细胞凋亡作用研究——新型强效抗乳腺癌药物。
Design, Synthesis, In vitro Cytotoxic Activity Evaluation, and Study of Apoptosis Inducing Effect of New Styrylimidazo[1,2-a]Pyridines as Potent Anti-Breast Cancer Agents.
机构信息
Institute of Biochemistry and Biophysics, Department of Biochemistry, University of Tehran, Tehran, Iran.
School of Chemistry, College of Science, University of Tehran, Tehran, Iran.
出版信息
Anticancer Agents Med Chem. 2019;19(2):265-275. doi: 10.2174/1871520618666180903100835.
BACKGROUND
This paper reports synthesis, cytotoxic activity, and apoptosis inducing effect of a novel series of styrylimidazo[1,2-a]pyridine derivatives.
OBJECTIVE
In this study, anti-cancer activity of novel styrylimidazo[1,2-a]pyridines was evaluated.
METHODS
Styrylimidazo[1,2-a]pyridine derivatives 4a-o were synthesized through a one-pot three-component reaction of 2-aminopyridines, cinnamaldehydes, and isocyanides in high yield. All synthesized compounds 4a-o were evaluated against breast cancer cell lines including MDA-MB-231, MCF-7, and T-47D using MTT assay. Apoptosis was evaluated by acridine orange/ethidium bromide staining, cell cycle analysis, and TUNEL assay as the mechanism of cell death.
RESULTS
Most of the synthesized compounds exhibited more potent cytotoxicity than standard drug, etoposide. Induction of apoptosis by the most cytotoxic compounds 4f, 4g, 4j, 4n, and 4m was confirmed through mentioned methods.
CONCLUSION
In conclusion, these results confirmed the potency of styrylimidazo[1,2-a]pyridines for further drug discovery developments in the field of anti-cancer agents.
背景
本文报道了一系列新型苯乙烯基咪唑并[1,2-a]吡啶衍生物的合成、细胞毒性活性和诱导细胞凋亡的作用。
目的
本研究评估了新型苯乙烯基咪唑并[1,2-a]吡啶的抗癌活性。
方法
通过 2-氨基吡啶、肉桂醛和异氰化物的一锅三步反应，以高产率合成了苯乙烯基咪唑并[1,2-a]吡啶衍生物 4a-o。所有合成的化合物 4a-o 均通过 MTT 法在乳腺癌细胞系 MDA-MB-231、MCF-7 和 T-47D 中进行了评估。通过吖啶橙/溴化乙锭染色、细胞周期分析和 TUNEL 分析评估细胞凋亡作为细胞死亡的机制。
结果
大多数合成的化合物比标准药物依托泊苷具有更强的细胞毒性。通过上述方法证实了最具细胞毒性的化合物 4f、4g、4j、4n 和 4m 诱导细胞凋亡。
结论
总之，这些结果证实了苯乙烯基咪唑并[1,2-a]吡啶在抗癌药物领域进一步药物发现开发中的潜力。
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