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

•Inspired by a novel spiropyrazolone antitumor scaffold, a series of derivatives were designed, synthesized and assayed.•Most spiropyrazolone derivatives showed good in vitro antitumor activity with a broad spectrum.•Compound 5k showed good antitumor activity and could effectively induce cancer cell apoptosis.

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.

Graphical abstractInspired by a novel spiropyrazolone antitumor scaffold, a series of spiropyrazolone derivatives were designed, synthesized and assayed for antitumor activity. Compound 5k showed good antitumor activity and could effectively induce cancer cell apoptosis.Figure optionsDownload full-size imageDownload as PowerPoint slide