Potential MRSA inhibitory activity of some new benzofuran-pyrazolo[1,5-a]pyrimidine hybrids attached to arene units via methylene or azo linkage

MRSA, a resistant bacteria causing severe infections, is targeted by researchers developing new anti-resistance compounds. The study aimed to investigate the MRSA inhibitory activity of two series of benzofuran-pyrazolo[1,5-a]pyrimidines 1 and 2, attached to arene units via methylene or azo linkage, respectively. The desired products were prepared, in 82–92% yields, by reacting benzofuran-based enaminone 4 with the appropriate 1H-pyrazole-3,5-diamines 5 in pyridine at reflux for 5–6 h. The new hybrids showed a wide spectrum of antibacterial activity against different ATCC strains. Products with azo linkage and para-substituted arene units with electron-releasing groups demonstrated higher antibacterial activity. 3-((4-Methoxyphenyl)diazenyl)-linked pyrazolo[1,5-a]pyrimidine 2e demonstrates activity that exceeded the reference ciprofloxacin with MIC/MBC values of 1.8/3.6 µM against S. aureus and E. coli strains. Also, it demonstrated more effective MRSA inhibitory activity than the reference linezolid, with MIC/MBC values of 3.6/14.4 and 1.8/7.2 µM against MRSA ATCC:33591 and ATCC:43300 strains, respectively.