Synthesis and characterization of novel 1,2,4-triazine derivatives with antiproliferative activity

A series of novel small molecules with a 1,2,4-triazine scaffold was obtained according to a recently published and highly efficient synthetic route. Screening for antiproliferative and cytotoxic activity revealed distinct anticancer effects against the human leukemia cell line K-562 combined with a remarkable low cytotoxicity. All compounds were in agreement with the ‘rule-of-five’ claims by Lipinski and calculated log Pcalc values were experimentally confirmed (log Pexp). For the most active compounds, in vitro serum albumin binding was investigated and structure–activity relationships were established.

A series of novel 1,2,4-triazin-5-ones was synthesized. Compound 3c shows promising antiproliferative effects on the human leukemia cell line (K-562), little cytotoxicity against HeLa, and fulfills very well the ‘rule-of-five’ claims by Lipinski for orally bioavailable drugs.Figure optionsDownload as PowerPoint slide