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Design Synthesis and In Vitro Mechanistic Investigation of Novel Hexacyclic Cage-Like Hybrid Heterocycles

机译:新型六环笼状杂种杂环的设计合成及体外机理研究

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摘要

Novel hexacyclic cage-like hybrid heterocycles have been synthesized in excellent yields employing a relatively less explored non-stabilized azomethine ylides derived from acenaphthenequinone and tyrosine with functionalized dipolarophiles using [3 + 2] cycloaddition strategy. The synthesized hexacyclic cage-like hybrid heterocycles were characterized by spectroscopic analysis. Following the physical characterization, these cage-like hybrid heterocycles were tested for their biological activity by means of different cancer (A549 and Jurkat cells) and non-cancer (BRL-3A and PCS-130) in vitro cell culture systems. The results of the study under tested concentrations (up to 100 μM) indicated that these compounds are not affecting any viability to the cell growth of non-cancer cells, while providing significant anticancer activity against both of the cancer cells. Further analysis of in-depth mechanistic study for the cell death indicated that these compounds are exhibiting late apoptosis or early necrosis pathway to the cells where it is operated by the induction of caspases.
机译:使用[3 + 2]环加成策略,使用相对较少探索的,由啶醌和酪氨酸衍生的带有功能化双极性亲和性的相对不稳定的偶氮甲亚胺,以高收率合成了新型六环笼状杂化杂环。通过光谱分析表征了合成的六环笼状杂合杂环。进行物理表征后,在体外细胞培养系统中,通过不同的癌症(A549和Jurkat细胞)和非癌症(BRL-3A和PCS-130)测试了这些笼状杂种杂环的生物活性。在测试浓度(最高100μM)下的研究结果表明,这些化合物对非癌细胞的细胞生长没有任何影响,同时提供了对两种癌细胞的显着抗癌活性。对于细胞死亡的深入机理研究的进一步分析表明,这些化合物向细胞展示晚期凋亡或早期坏死途径,并通过胱天蛋白酶诱导其运作。

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