Synthesis and antitumor evaluation of a novel series of triaminotriazine derivatives

A series of triaminotriazine derivatives (compounds 5a–f, 6a–x, and 7a–g) was designed, synthesized, and evaluated for their inhibition activities to colorectal cancer (CRC) cell lines (HCT-116 and HT-29). Most of the synthesized compounds demonstrated moderate anti-proliferatory effects on both HCT-116 and HT-29 cell lines at the concentration of 10 μM. The inhibitory activities against HCT-116 and HT-29 cell lines were discussed to develop the structure–activity relationships of this new series. Compounds 6l and 6o exhibited prominent inhibition activities toward HCT-116, with IC50s of 0.76 and 0.92 μM, respectively. The in vivo antitumor studies and pharmacokinetics of compound 6l showed that it might be a promising new hit for further development of antitumor agents.

By structural modification of the screening hit (4,6-bis(N-morpholino)-[1,3,5]triazin-2-yl)-phenylamine (5a), four compounds exhibited higher inhibition activities against HCT-116 with IC50 values below 5 μM. Compounds 6l and 6o were most prominent against HCT-116, with IC50s of 0.76 and 0.92 μM, respectively.Figure optionsDownload as PowerPoint slide