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螺环氧化吲哚-吡咯烷杂环混合物通过激活 caspase-3 促进细胞凋亡。

Spirooxindole-pyrrolidine heterocyclic hybrids promotes apoptosis through activation of caspase-3.

机构信息

Department of Chemistry, College of Science, King Saud University, P.O. Box 2455, Riyadh 11451, Saudi Arabia.

Department of Chemistry, College of Science, King Saud University, P.O. Box 2455, Riyadh 11451, Saudi Arabia.

出版信息

Bioorg Med Chem. 2019 Jun 15;27(12):2487-2498. doi: 10.1016/j.bmc.2019.03.011. Epub 2019 Mar 5.

Abstract

A small library of spirooxindole-pyrrolidine hybrids have been synthesized for the first time in an ionic liquid, [bmim]Br in good to excellent yields employing a new class of non-stabilized azomethine ylides derived from isatin and tyrosine, a combination that has been rarely employed for the in situ generation of azomethine ylides using [3+2] cycloaddition strategy. Following the synthesis and characterization of the spirooxindole-pyrrolidine heterocyclic hybrids, they were tested for their anticancer activity as against the changes in the concentrations and time periods with different in vitro cell cultures containing cancer and non-cancer cells, where the results revealed for a potential therapeutic activity. Further analysis for the mechanism of cell death by the cancer cells indicated for the caspase-dependent apoptotic pathway, specifically mediated by caspase-3. Based on these results, it can be demonstrated that the synthesized spirooxindole-pyrrolidine hybrids may serve as one of the better therapeutic agents used for the treatment of malignant tumors.

摘要

首次在离子液体 [bmim]Br 中成功合成了一小部分螺环氧化吲哚-吡咯烷杂合体系,产率良好至优秀,采用了一种新型的非稳定亚甲胺叶立德,由色胺和酪氨酸衍生而来,这种组合很少用于使用 [3+2] 环加成策略原位生成亚甲胺叶立德。在合成和表征螺环氧化吲哚-吡咯烷杂环杂合体系后,对其进行了抗癌活性测试,针对不同的体外细胞培养物中含有的癌细胞和非癌细胞的浓度和时间周期的变化进行了测试,结果显示出潜在的治疗活性。对癌细胞死亡机制的进一步分析表明,细胞凋亡途径是 caspase 依赖性的,特别是由 caspase-3 介导的。基于这些结果,可以证明合成的螺环氧化吲哚-吡咯烷杂合体系可用作治疗恶性肿瘤的较好治疗剂之一。

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