Abstract

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

摘要

β-内酰胺酶是催化 β-内酰胺环水解的酶，导致 β-内酰胺抗生素功能丧失。在本报告中，在体外和计算机中研究了基于基团的选定芳香族化合物（尤其是含有黄酮环）对 β-内酰胺酶的抑制作用。为此，研究了7-羟基-4'-硝基异黄酮、杨梅素、芒柄花素、3-甲基黄酮-8-羧酸、6-氟黄酮和咖啡酸对蜡状芽孢杆菌β-内酰胺酶酶活性的抑制作用。这些化合物的IC ₅₀值经测定为53至346 mM。7-羟基-4'-硝基异黄酮、芒柄花素和杨梅素抑制具有 K _i的酶值分别为 27.65 ± 4.22、58.92 ± 12.83 和 67.42 ± 5.77 µM。为了评估活性化合物的潜在酶结合位置，进行了对接研究。除了动力学和计算机研究外，还测试了化合物与青霉素对肺炎克雷伯菌(ATCC 700603) 和大肠杆菌(ATCC 35128)的协同作用。我们的结果表明，与青霉素结合的7-羟基-4'-硝基异黄酮、3-甲基黄酮-8-羧酸和杨梅素完全阻止了细菌的生长。

由 Ramaswamy H. Sarma 传达