Synthesis, antitrypanosomal activity and molecular docking studies of pyrimidine derivatives

This publication describes the synthesis of 28 pyrimidine derivatives of which eight are new. Their structures have been verified by spectroscopic techniques (IR, H1, C13 NMR data). The mass spectral analysis gave correctly the elemental compositions of all compounds. All 28 compounds have been evaluated in vitro against two different stages of Trypanosoma cruzi: 1. epimastigote and 2. trypomastigotes. Compounds 3a, 3b, 3j, 3k, 3o, 3s and 5d presented greater activity than benznidazole(BZN) for trypomastigotes. Compound 3a selectivity was similar to that of BZN. Molecular modeling using the Docking approach was performed to determine binding of the ligand to the enzyme. The M.O. calculations using the GOLD 5.2 program provided information on the pyrimidine binding sites with the enzyme.