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Stereoselective Assembly of Multifunctional Spirocyclohexene Pyrazolones That Induce Autophagy-Dependent Apoptosis in Colorectal Cancer Cells

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journal contribution
posted on 25.06.2019, 00:00 by Xiang Li, Fei-Yu Chen, Jing-Wen Kang, Jin Zhou, Cheng Peng, Wei Huang, Mu-Ke Zhou, Gu He, Bo Han
Enantio- and diastereoselective synthesis of multifunctional spiropyrazolone scaffolds has been achieved using secondary amine-catalyzed [4 + 2] annulations of α,β,γ,δ-unsaturated pyrazolones with aldehydes. The pyrazolone substrates serve as C4 synthons to produce 6-membered, carbocycle-based, chiral spiropyrazolone derivatives. The synthesized chiral compounds showed potent toxicity against a panel of cancer cell lines. The most potent compound 3h-induced cell cycle arrest and macroautophagy in HCT116 colorectal cancer cells, triggering autophagy-dependent apoptotic cell death.