Synthesis, biological activity and modeling study of some thiopyrimidine derivatives and their platinum(II) and ruthenium(III) metal complexes

Abstract

Abstract A new series of 6-amino-5-(aryldiazenyl)-N 1,N 3-dimethyl-2-thioxo-pyrimidin-4-one derivatives 17–27 and the N 1-methyl-azothiopyrimidine analog 28 were synthesized from the pyrimidine derivatives 4 and 5, respectively, via diazotization reaction, with various amines. The platinum(II) metal complexes [bis(4-amino-N 3-methyl-6-oxo-2-thioxo-pyrimidin-1-yl)]Pt(II) (29) and [(6-amino-5-(4-R-phenyl)diazenyl)-N 1 ,N 3-dimethyl-2-thioxo-pyrimidin-4-one)]Pt(II)Cl2 derivatives 30–33 were prepared from the treatment of 5 and the azo analogs 17 and 21–23 with PtCl2, respectively. Analogously, 5 and 17 were treated with RuCl3·3H2O to give the Ru(III) complexes 34 and 35, respectively. The newly synthesized compounds were assayed against HIV-1 and HIV-2 in MT-4 cells. The results revealed that 26 and 30 were the only compounds in the series inhibiting HIV replication in cell cultures with an IC50 value of >2.07 and >3.02 μg mL–1, respectively. The molecular modeling interactions of 26 with some amino acids of HIV reverse transcriptase were studied. In addition, the antibacterial activity of 17–35 and 31–33 against Staphylococcus aureus and Escherichia coli was evaluated.