Synthesis and antibacterial evaluation of some pyrimidine hybrids as potential MRSA inhibitors

Research on developing new treatments for methicillin-resistant Staphylococcus aureus (MRSA), which is extremely dangerous, is a major concern. New aryl-linked 2,4-diaminopyrimidine-5-carboxamides 1 and their bis-analogues connected to various spacers 2 were prepared herein and examined as possible anti-MRSA inhibitors. These hybrids are efficiently prepared by reacting a ternary mixture of pyrimidine-linked 2-cyanoacetamide and guanidine nitrate with the suitable aromatic aldehydes or bis(aldehydes). The reaction was carried out in DMSO at reflux for 5-8 h containing anhydrous potassium carbonate. The alkane-linked bis-products 2b-2e displayed promising potency, with MIC and MBC ranging from 2.21-2.33 and 4.43-4.66 µM, respectively, against S. aureus and E. coli. Moreover, the hexane-linked bis-product 2e showed significant anti-MRSA activity with MIC/MBC of 2.21/8.87 µM. In the presence of an S9 mixture, the Ames test showed that 2b-2e are not mutagenic to Salmonella strains.