Synthesis and antibiofilm activity of 1,2,3-triazole-pyridine hybrids against methicillin-resistant Staphylococcus aureus (MRSA)

Antibiotic-resistant bacteria are emerging at an alarming rate, posing a potential threat to human health. We synthesised alkyne-functionalised pyridines 3 and 4via alkylation of substituted 2-oxo-1,2-dihydropyridine derivatives 1 and 2 with propargyl bromide in alkaline DMF. The reactions afforded the O-propagylated compounds 3 and 4 as the main products. Copper(i)-catalysed azide-alkyne cycloaddition of compounds 3 and 4 with aromatic azides furnishes compounds 11-22. The chemical structures of the 1,2,3-triazole-pyridine hybrids 11-22 were fully verified using different spectroscopic tools, such as FT-IR, H-1 NMR, C-13 NMR, and 2D NMR. We evaluated in vitro antibacterial and antibiofilm activities of the 1,2,3-triazole-pyridine hybrids 11-22 against methicillin-resistant Staphylococcus aureus (MRSA) in both planktonic and sessile cells. Compounds 17, 18, and 21 exhibited promising growth inhibition activity against planktonic and sessile MRSA cells with IC50 = 34.94, 37.91, and 43.88 mu M, respectively. The antibiofilm activities of the new compounds were evaluated using Vancomycin (Van) as a standard reference drug (IC50 186.0 mu M).

Automated summary

A series of new compounds with antibacterial properties were synthesized by the research team, and their inhibitory and antibiofilm activities against methicillin-resistant Staphylococcus aureus (MRSA) were evaluated. The results showed that some compounds exhibited significant growth inhibition activity against MRSA cells, with antibiofilm effects superior to Vancomycin.