Design, synthesis and evaluation of novel diaryl urea derivatives as potential antitumor agents

•Twenty seven novel diaryl ureas were designed and synthesized.•Their antitumor activity against five cancer cell lines was evaluated.•Compound 23 demonstrated broad-spectrum antitumor activity in vitro.•Compound 23 was subjected to docking analysis on B-Raf.•Compound 23 was screened for Raf kinase inhibition.

A novel series of diaryl ureas containing different linker groups were designed and synthesized. Their in vitro antitumor activity against MX-1, A375, HepG2, Ketr3 and HT-29 was evaluated using the standard MTT assay. Compounds having a rigid linker group such as vinyl, ethynyl and phenyl showed significant inhibitory activity against a variety of cancer cell lines. Specifically, compound 23 with a phenyl linker group demonstrated broad-spectrum antitumor activity with IC50 values of 5.17–6.46 μM against five tested tumor cell lines. Compound 23 is more potent than reference drug sorafenib (8.27–15.2 μM), representing a promising lead for further optimization.

Graphical abstractA series of diaryl urea derivatives containing different linker groups were designed and synthesized. Compound 23 demonstrated broad-spectrum antitumor activity in vitro.Figure optionsDownload full-size imageDownload as PowerPoint slide