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一锅法三组分合成及高度功能化螺环吲哚-吡咯烷杂环类化合物体外抗肿瘤活性的机制研究。

A One-Pot Three-Component Synthesis and Investigation of the In Vitro Mechanistic Anticancer Activity of Highly Functionalized Spirooxindole-Pyrrolidine Heterocyclic Hybrids.

机构信息

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

出版信息

Molecules. 2020 Nov 27;25(23):5581. doi: 10.3390/molecules25235581.

Abstract

With an aim to develop more effective and affordable anticancer agents possessing a unique mechanism of action, we designed and synthesized derivatives of spirooxindole-pyrrolidine heterocyclic hybrids in good yields through a one-pot three-component (3+2) cycloaddition strategy. The synthesized compounds were characterized thoroughly for the physicochemical properties by making use of FT-IR, NMR spectroscopy, and mass spectrometry. Further, these compounds have been evaluated for the influence of anticancer activity against HepG2 cells up to 200 µg/mL concentration. The highly active molecular scaffold was tested for the in-depth mechanistic studies, and it was found that the major pathway of cell death is apoptosis which occurs through the induction of reactive oxygen species followed by the involvement of caspases.

摘要

为了开发更有效和更经济实惠的、具有独特作用机制的抗癌剂,我们设计并通过一锅法 3+2 环加成策略,以较高产率合成了螺环氧化吲哚-吡咯烷杂环类化合物的衍生物。通过傅里叶变换红外光谱(FT-IR)、核磁共振波谱(NMR)和质谱(MS)等方法,对所合成的化合物进行了全面的理化性质表征。此外,我们还评估了这些化合物对 HepG2 细胞的抗癌活性,其浓度高达 200μg/mL。对高活性分子支架进行了深入的机制研究,结果发现细胞死亡的主要途径是凋亡,这是通过诱导活性氧继而涉及半胱天冬酶来实现的。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3a5d/7730040/4ab31d2b5f44/molecules-25-05581-sch001.jpg

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