Highly functionalized pyrrolidine analogues: stereoselective synthesis and caspase-dependent apoptotic activity

高度功能化的吡咯烷类似物:立体选择性合成和 caspase 依赖性凋亡活性

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作者:Raju Suresh Kumar, Abdulrahman I Almansour, Natarajan Arumugam, Faruq Mohammad, Waleed Shihan Alshahrani, Kotresha D, Mohammad Altaf, Mohammad Azam, J Carlos Menéndez

Abstract

Novel spiropyrrolidine heterocyclic hybrids were synthesized for the first time in a sustainable fashion employing a 1,3-dipolar cycloaddition strategy to form a new class of azomethine ylides generated from tyrosine and acenaphthenequinone. Following their synthesis and characterization, these heterocyclic hybrids were tested for their anticancer activities by incubation at different concentrations and durations with different cancer and non-cancer cell cultures, and the results indicated a potential therapeutic activity. Further analysis of cancer cell death revealed that it occurred through a caspase-related apoptotic pathway, specifically mediated by caspase-3. These results demonstrated that the obtained spiropyrrolidine heterocyclic hybrids may be good hit compounds for the development of potential therapeutic agents for the treatment of malignant tumors.

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