Pyrimidine‐Containing Amino Acid Derivatives as New Anticancer Agents

Derivatives of natural amino acid hold promise as starting point for drug discovery. We synthesized five pyrimidine‐containing derivatives of natural amino acids 1a ‐ e using green condition and seven of their N ‐aryl amide adducts 2a ‐ g using amide coupling. The synthesized compounds were screened for anticancer activity using MTT assay on HepG2 cell line. The results showed that fragment‐like compounds 1a ‐ c were more potent and reached low µM IC 50 of 18‐25 µM. Moreover, the best compound 1a inhibited significantly 3D tumorsphere formation and cell migration. Docking studies of 1a‐c suggest their HepG2 antiproliferative activity could be mediated via multikinase inhibition of p38α, VEGFR2 and FGFR‐1. 1a‐c is a good starting point to develop more potent compounds with excellent calculated physico chemical properties.