Synthesis and in vitro activity in HCT116 human colon cancer cells of new 4-substituted-pyrimido[5,4-d]pyrimidine derivatives

Abstract

Pyrimidopyrimidines 1 [Fig.1] are a fused heterocyclic system of interest in the context of drug discovery and development that has attracted considerable interest in recent years mainly due to their wide range of pharmacological activity. In the literature pyrimidopyrimidines are reported as anti-tumour1, antiviral1,2, antioxidant3, antifungal4 and hepatoprotective5 agents.1–7The most known derivative of this family is dipyridamole2, a 2, 4, 6, 8-tetrasubstituted pyrimidopyrimidine that is marketed as a coronary vasodilator.7,8 Recently, in our research group, under our program of drug discovery, pyrimidopyrimidines were identified as potent anticancer agents9. The initial SAR analysis showed that the activity depends on the substituents R and R2. Herein, we report the synthesis of new pyrimido[5,4-d]pyrimidines derivatives, that are obtained from 4-hydrazinepyrimidopyrimidine 3 by reaction with aldehydes and anhydrides. The in vitro activity in HCT116 human colon cancer cells will also be presented.