Efficient Synthesis of 2,3'-Spirobi (Indolin)-2'-Ones and Preliminary Evaluation of Their Damage to Mitochondria in HeLa Cells

Huajie Li; Zhenjie Yu; Haoyi Sun; Bo Liu; Xin Wang; Zhe Shao; Meiling Wang; Weilin Xie; Xingang Yao; Qingqiang Yao; Ying Zhi

doi:10.3389/fphar.2021.821518

Efficient Synthesis of 2,3'-Spirobi (Indolin)-2'-Ones and Preliminary Evaluation of Their Damage to Mitochondria in HeLa Cells

Front Pharmacol. 2022 Feb 23:12:821518. doi: 10.3389/fphar.2021.821518. eCollection 2021.

Authors

Huajie Li^{1

2}, Zhenjie Yu^{1

2}, Haoyi Sun^{1

2}, Bo Liu^{1

2}, Xin Wang^{1

2}, Zhe Shao^{1

2}, Meiling Wang^{1

2}, Weilin Xie^{1

2}, Xingang Yao³, Qingqiang Yao^{1

2}, Ying Zhi^{1

2}

Affiliations

¹ School of Pharmacy and Pharmaceutical Sciences, Shandong First Medical University, Jinan, China.
² Institute of Materia Medica, Shandong Academy of Medical Sciences, Jinan, China.
³ School of Pharmaceutical Sciences, Southern Medical University, Guangzhou, China.

Abstract

A novel formal (4 + 1) annulation between N-(o-chloromethyl)aryl amides and 3-chlorooxindoles through in situ generated aza-ortho-QMs with 3-chlorooxindoles is reported for the synthesis of a series of 2,3'-spirobi (indolin)-2'-ones in high yields. Under structured illumination microscopy, compound 3a is found to change the mitochondrial morphology and induce mitophagy pathway, which might then trigger mitophagy in cancer cells.

Keywords: annulation; aza-ortho-quinone methides; mitochondria; morphology; spirooxindole.