Novel spiropyrazolone antitumor scaffold with potent activity: Design, synthesis and structure-activity relationship

Eur J Med Chem. 2016 Jun 10:115:141-7. doi: 10.1016/j.ejmech.2016.03.039.

Shanchao Wu ¹, Yu Li ¹, Guixia Xu ², Shuqiang Chen ¹, Yongqiang Zhang ¹, Na Liu ¹, Guoqiang Dong ¹, Chaoyu Miao ¹, Hua Su ³, Wannian Zhang ⁴, Chunquan Sheng ⁵

Affiliations

1 School of Pharmacy, Second Military Medical University, 325 Guohe Road, Shanghai 200433, China.
2 Clinical Research Center, Changhai Hospital, Second Military Medical University, Shanghai 200433, China.
3 Department of Pharmaceutics, Jinling Hospital, Nanjing University School of Medicine, Nanjing 210002, China. Electronic address: suhuash@sina.com.
4 School of Pharmacy, Second Military Medical University, 325 Guohe Road, Shanghai 200433, China. Electronic address: zhangwnk@hotmail.com.
5 School of Pharmacy, Second Military Medical University, 325 Guohe Road, Shanghai 200433, China. Electronic address: shengcq@hotmail.com.

PMID: 27016707 DOI: 10.1016/j.ejmech.2016.03.039

Abstract

Phenotypic screening of high quality compound library is an effective strategy to discover novel bioactive molecules. Previously, we developed the divergent organocatalytic cascade approach to efficiently construct a focused library with scaffold diversity and successfully identified a novel spiropyrazolone antitumor scaffold. Herein, a series of spiropyrazolone derivatives were designed, synthesized and assayed. Most of them showed good in vitro antitumor activity with a broad spectrum. Preliminary structure-activity relationship for the substitutions and the stereo configuration were obtained. Compound 5k showed good antitumor activity and could effectively induce Cancer cell Apoptosis, which represents a good starting point for the development of novel antitumor agents.

Keywords

Antitumor; Cancer cell apoptosis; Spiropyrazolone; Structure–activity relationship.

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