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新型螺吡咯烷杂环化合物作为抗癌药物的作用机制探索

Mechanistic Exploration of Novel Spiropyrrolidine Heterocyclic Hybrids as Anticancer Agents.

作者信息

Kumar Raju Suresh, Almansour Abdulrahman I, Arumugam Natarajan, Mohammad Faruq, Kumar Raju Ranjith

机构信息

Department of Chemistry, College of Science, King Saud University, Riyadh, Saudi Arabia.

Department of Organic Chemistry, School of Chemistry, Madurai Kamaraj University, Madurai, India.

出版信息

Front Chem. 2020 Jun 3;8:465. doi: 10.3389/fchem.2020.00465. eCollection 2020.

Abstract

Novel spiro acenaphthylene pyrrolo[1,2-]isoquinoline/pyrrolidine hybrids have been achieved through Pictet-Spengler/Eschweiler-Clarke reactions depending on the substitution in the benzyl ring. The biological efficacy of -methyl spiropyrrolidine derivatives toward different cancer and non-cancer cell lines revealed that these novel spiro heterocyclic hybrids induced cancer cell death at moderate concentrations, while slight reduction in non-cancer cell viability at the higher concentrations. The analysis of cancer cells proved that the major pathway of cell death is apoptosis and in addition, the role of caspases is confirmed by the appearance of fluorescent cells in microscopic images. Therefore, this study indicates a sustainable way of treating cancer cells by inducing apoptotic pathways and associated caspases, while simultaneously protecting the non-cancer cells.

摘要

通过皮克特-施彭格勒反应/埃施魏勒-克拉克反应,依据苄环上的取代情况,已成功合成了新型螺苊烯并吡咯并[1,2 -]异喹啉/吡咯烷杂化物。对甲基螺吡咯烷衍生物针对不同癌细胞系和非癌细胞系的生物学功效研究表明,这些新型螺杂环杂化物在中等浓度下可诱导癌细胞死亡,而在较高浓度时非癌细胞活力略有下降。对癌细胞的分析证明,细胞死亡的主要途径是凋亡,此外,通过显微镜图像中荧光细胞的出现证实了半胱天冬酶的作用。因此,本研究表明了一种通过诱导凋亡途径和相关半胱天冬酶来治疗癌细胞的可持续方法,同时保护非癌细胞。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c5c0/7283928/453b7718fd9d/fchem-08-00465-g0005.jpg

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