Enhancing bactericidal strategy with selected aromatic compounds: in vitro and in silico study

β-Lactamases are enzymes that catalyze the hydrolysis of the β-lactam ring, resulting in loss of function in β-lactam antibiotics. In this report, the inhibition of β-lactamase enzyme by group-based selected aromatic compounds, especially containing flavone ring, was investigated in vitro and in silico. For this purpose, the inhibitory effects of 7-hydroxy-4'-nitroisoflavone, myricetin, formononetin, 3-methylflavone-8-carboxylic acid, 6-fluoroflavone and caffeic acid on β-lactamase from Bacillus cereus enzyme activity were investigated. IC₅₀ values of these compounds were determined to range from 53 to 346 mM. 7-hydroxy-4'-nitroisoflavone, formononetin and myricetin inhibited the enzyme with the K_i values of 27.65 ± 4.22, 58.92 ± 12.83 and 67.42 ± 5.77 µM, respectively. To evaluate the potential enzyme binding positions of the active compounds, docking studies were performed. In addition to kinetic and in silico studies, the synergistic effects of the compounds with penicillin on Klebsiella pneumoniae (ATCC 700603) and Escherichia coli (ATCC 35128) were tested in vitro. Our results indicated that 7-hydroxy-4'-nitroisoflavone, 3-methylflavone-8-carboxylic acid and myricetin that combined with penicillin completely precluded the bacterial growth.Communicated by Ramaswamy H. Sarma.