Subhi Hanan Tariq, Fatah Hiwa Ramadhan, Muhammad Hanaa Ali
Department of Biology, Faculty of Science and Health, Koya University, Koya KOY45, Kurdistan Region-F.R., Iraq.
Can J Infect Dis Med Microbiol. 2022 Jul 13;2022:6720241. doi: 10.1155/2022/6720241. eCollection 2022.
Although the structure-activity relationship indicates that the 4-thioxoimidazolidin ring is essential for antibacterial activities and pharmaceutical applications, there were no enough studies on the derivatives of this compound. Evaluating the new hydantoin compounds C5 (3-((2-bromobenzylidene) amino)-2- thioxoimidazolidin-4-one) and C6 (3-((4- methoxybenzylidene) amino)-2-thioxoimidazolidin-4-one) that were prepared against clinical isolates for antibacterial, antibiofilm, and antihemagglutination activities is the aim of this study. Therefore, the potential clinical resistance of the strains was evaluated by their ability to form biofilms, antibiotic resistance, and agglutinate erythrocytes macroscopically and microscopically; besides, the bacterial biofilm was screened for any association with the patient's serum immunoglobulin levels and complements. Despite the effective concentration for C5 and C6 compounds, which is ≤ 31.25 g/ml, the reduction rate is not concentration-dependent; it depends on the molecular docking of the hydantoin compounds. Hence, the effect of the minimal inhibitory concentrations (MICs) is variable. In this study, the results for the compounds (with the concentration of 31.25-62.5 g/mL for C5 and 62.5-125 g/mL for C6) significantly manifest the antibacteria, antibiofilm, and antihemagglutination effects against the virulent strains of due to the high percentage of biofilm inhibition that was caused by the new hydantoin compounds. Besides, time-kill kinetics studies showed that these compounds pose bactericidal action. Overall, this study revealed that the new hydantoin derivatives have an interesting potential as new antibacterial drugs through the inhibition of bacterial adhesion. The infections of these isolates activate the complement system through the lectin pathway. Nevertheless, these compounds can be improved in order to be used at even lower concentrations.
尽管构效关系表明4-硫代咪唑啉环对抗菌活性和药物应用至关重要，但对该化合物的衍生物却缺乏足够的研究。本研究旨在评估新制备的乙内酰脲化合物C5（3-((2-溴亚苄基)氨基)-2-硫代咪唑啉-4-酮）和C6（3-((4-甲氧基亚苄基)氨基)-2-硫代咪唑啉-4-酮）对临床分离株的抗菌、抗生物膜和抗血凝活性。因此，通过菌株形成生物膜的能力、抗生素抗性以及在宏观和微观上凝集红细胞的能力来评估菌株的潜在临床抗性；此外，还筛查了细菌生物膜与患者血清免疫球蛋白水平和补体之间的任何关联。尽管C5和C6化合物的有效浓度≤31.25μg/ml，但其降低率并非浓度依赖性；它取决于乙内酰脲化合物的分子对接。因此，最小抑菌浓度（MIC）的效果是可变的。在本研究中，化合物（C5浓度为31.25 - 62.5μg/mL，C6浓度为62.5 - 125μg/mL）的结果显著显示出对致病菌株的抗菌、抗生物膜和抗血凝作用，这是由于新的乙内酰脲化合物引起的生物膜抑制百分比很高。此外，时间 - 杀菌动力学研究表明这些化合物具有杀菌作用。总体而言，本研究表明新的乙内酰脲衍生物通过抑制细菌黏附作为新型抗菌药物具有有趣的潜力。这些分离株的感染通过凝集素途径激活补体系统。然而，可以对这些化合物进行改进以便在更低的浓度下使用。
