Simijonović Dušica, Avdović Edina, Milić Sandra Jovičić, Antonijević Marko, Milenković Dejan, Marković Katarina, Grujović Mirjana, Stojković Danijela Lj, Dekić Milan, Marković Zoran
Department of Science, Institute for Information Technologies, University of Kragujevac, Jovana Cvijića bb, 34000 Kragujevac, Serbia.
Department of Natural Science and Mathematics, State University of Novi Pazar, Vuka Karadžića 9, 36300 Novi Pazar, Serbia.
Pharmaceutics. 2024 Nov 18;16(11):1472. doi: 10.3390/pharmaceutics16111472.
The aim of this study is to present the synthesis of two new compounds with promising antimicrobial and anti-inflammatory properties using precursors that contain pyrogallol and coumarin units. The characterization of the obtained compounds () ()-'-(1-(2,4-dioxochroman-3-ylidene)ethyl)-2,3,4-trihydroxybenzohydrazide () and ()-'-(1-(2,4-dioxochroman-3-ylidene)ethyl)-3,4,5-trihydroxybenzohydrazide () was performed using various spectroscopic methods in combination with the DFT methods. To evaluate antimicrobial and anti-inflammatory activities, were tested against 13 different types of microorganisms and soybean lipoxygenase. To determine the specific mechanisms of anti-LOX activity, molecular docking and molecular dynamics studies were performed. These compounds had the most potent antibacterial activity against the bacterium ATCC 12453, with a MIC value of 31.125 µg/mL. In addition, three standard bacterial species were chosen to evaluate the antibiofilm activity of tested substances. The results showed that the strongest effect of was noticed on the biofilm formation of ATCC 25923 (BIC at 378 µg/mL). The anti-LOX results indicate that have excellent activity with the IC value for = 38.12 μM and = 34.12 μM. The obtained in vitro and in silico results confirm the strong inhibitory potential of the investigated compounds.
本研究的目的是使用含有连苯三酚和香豆素单元的前体，合成两种具有抗菌和抗炎特性的新化合物。使用各种光谱方法结合密度泛函理论（DFT）方法对所得化合物（）（）-'-(1-(2,4-二氧代苯并二氢吡喃-3-亚基)乙基)-2,3,4-三羟基苯甲酰肼（）和（）-'-(1-(2,4-二氧代苯并二氢吡喃-3-亚基)乙基)-3,4,5-三羟基苯甲酰肼（）进行了表征。为了评估抗菌和抗炎活性，对13种不同类型的微生物和大豆脂氧合酶进行了测试。为了确定抗脂氧合酶活性的具体机制，进行了分子对接和分子动力学研究。这些化合物对ATCC 12453细菌具有最强的抗菌活性，最低抑菌浓度（MIC）值为31.125μg/mL。此外，选择了三种标准细菌菌株来评估受试物质的抗生物膜活性。结果表明，对ATCC 25923的生物膜形成影响最强（生物膜抑制浓度（BIC）为378μg/mL）。抗脂氧合酶结果表明，具有优异的活性，的半数抑制浓度（IC）值为38.12μM，的为34.12μM。体外和计算机模拟结果证实了所研究化合物具有很强的抑制潜力。
