Synthesis of novel heterocyclic compounds containing pyrimidine nucleus using the Biginelli reaction: Antiproliferative activity and docking studies

In a single reaction step, pyrimidine derivatives (4a‐p) were synthesized from the triple reaction of aromatic aldehydes (1), ethyl cyanoacetate (2), and some guanyl hydrazone derivatives (3a‐n). These compounds were tested as in vitro against two types of cancerous cell lines, namely, a human colon cancerous cell line (DLD‐1) and a human breast cancerous cell line (MDA‐MB‐231). According to the obtained results, nearly all the compounds have cytotoxic activity in the tested cell lines. Especially, the compounds 4j, 4k, and 4n had a significant effect against DLD‐1. Furthermore, compounds 4g, 4m, and 4o exhibited lower IC50 values compared to other synthesized compounds against MDA‐MB‐231. We hope that these compounds can be improved as anticancer agents in the future. Molecular docking was performed according to both topoisomerase I and N‐acetyltransferase 1 proteins to examine theoretically the binding mode and site of pyrimidine compounds having the best activity.