Following the appearance of several antimicrobial agents to control the spread of infections, two major challenges have emerged: (i) the occurrence and blowout of multiresistant bacteria and the increase of chronic diseases and (ii) difficult‐to‐eradicate infections. In this study, we tested five benzoylthiourea derivatives for their ability to inhibit and stop bacterial growth and evaluated the possible influence of 1,2,4‐triazolyl‐benzoylthiourea derivative 4 on the formation and eradication of Staphylococcus aureus biofilms. Benzoylthiourea derivatives 4, 6, 10, 11 and 13 were obtained in one or two steps with low cost and subjected to tests to identify their minimum inhibitory concentration (MIC) and minimum bactericidal concentration. In vitro tests were also performed to assess their effects on biofilm formation and in preformed biofilms and scanning electron microscopy was used to visualize the effects on biofilm formation. The 1,2,4‐triazolyl‐benzoylthiourea derivative 4 showed bacteriostatic activity against the S. aureus HU25 clinical strain with an MIC of 16 µg ml−1, which is below the toxic concentration (at 2500 µg ml−1, 62·25% of the cells remained viable). Compound 4 also effectively prevented biofilm formation at the three subinhibitory concentrations tested (1/2 MIC, 1/4 MIC and 1/8 MIC) as confirmed by scanning electron microscopy. For breakdown of formed biofilms, the main influence was at a subinhibitory concentration (1/2 MIC). These findings make compound 4 a strong candidate for studies on the development of new antimicrobial and antibiofilm agents.

中文翻译：

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苯甲酰硫脲衍生物的合成及其对浮游金黄色葡萄球菌及其生物膜的抗菌性能分析

随着几种控制感染传播的抗菌药物的出现，出现了两个主要挑战：（i）多重耐药菌的发生和爆发以及慢性病的增加；（ii）难以根除的感染。在这项研究中，我们测试了五种苯甲酰硫脲衍生物抑制和阻止细菌生长的能力，并评估了 1,2,4-三唑基-苯甲酰硫脲衍生物 4 对金黄色葡萄球菌生物膜形成和根除的可能影响。苯甲酰硫脲衍生物 4、6、10、11 和 13 是通过一两步低成本获得的，并进行测试以确定它们的最低抑菌浓度 (MIC) 和最低杀菌浓度。还进行了体外测试以评估它们对生物膜形成和预制生物膜的影响，并使用扫描电子显微镜观察对生物膜形成的影响。1,2,4-三唑基-苯甲酰硫脲衍生物 4 对金黄色葡萄球菌 HU25 临床菌株显示出抑菌活性，MIC 为 16 µg ml-1，低于毒性浓度（2500 µg ml-1，62·25 ％的细胞保持活力）。扫描电子显微镜证实，化合物 4 在测试的三个亚抑制浓度（1/2 MIC、1/4 MIC 和 1/8 MIC）下也有效地阻止了生物膜的形成。对于形成的生物膜的分解，主要影响是亚抑制浓度（1/2 MIC）。这些发现使化合物 4 成为研究开发新型抗菌剂和抗生物膜剂的有力候选者。