Design, synthesis, and exploration of antibacterial activity of 6-1,2-oxazin-6-ones

This study reports the in silico design of 30 6 H -1,2-oxazin-6-ones against DHFR and PTC antimicrobial targets. Docking compounds 1 , 3 , 4 , 6 , and 8 with both enzymes was favorable, outperforming Trimethoprim with DHFR. Therefore, 12 6 H -1,2-oxazin-6-ones, including the most promising compounds, were synthesized through an aminolysis reaction of β-cyanoketones with hydroxylamine hydrochloride, obtaining moderate to high yields (55-88%). Subsequently, antibacterial studies were conducted against five bacteria: four Gram-positive MRSA (ATCC 43300 and three clinical isolates) and one Gram-negative ( E. coli ATCC 25922). Compounds 1 , 2 , 3 , 4 , 6 , and 8 inhibited bacterial growth with MIC values ranging from 3.125 to 200 μg mL −1 . Compound 1 showed better activity against Gram-positive bacteria than Linezolid. Toxicity assays indicated no adverse effects of the active oxazinones in silico and in vitro . This study demonstrated the antibacterial potential of the selected 6 H -1,2-oxazin-6-ones against resistant human pathogenic bacteria. This study reports the in silico design of 30 6 H -1,2-oxazin-6-ones against DHFR and PTC antimicrobial targets.