PDF(Pubmed)
Abstract：
Novel antimicrobial agents are needed to combat antimicrobial resistance. This study tested novel pentafluorosulfanyl-containing triclocarban analogs for their potential antibacterial efficacy. Standard procedures were used to produce pentafluorosulfanyl-containing triclocarban analogs. Twenty new compounds were tested against seven Gram-positive and Gram-negative indicator strains as well as 10 clinical isolates for their antibacterial and antibiofilm activity. Mechanistic investigations focused on damage to cell membrane, oxidizing reduced thiols, iron-sulfur clusters, and oxidative stress to explain the compounds\' activity. Safety profiles were assessed using cytotoxicity experiments in eukaryotic cell lines. Following screening, selected components had significantly better antibacterial and antibiofilm activity against Gram-positive bacteria in lower concentrations in comparison to ciprofloxacin and gentamycin. For instance, one compound had a minimum inhibitory concentration of <0.0003 mM, but ciprofloxacin had 0.08 mM. Mechanistic studies show that these novel compounds do not affect reduced thiol content, iron-sulfur clusters, or hydrogen peroxide pathways. Their impact comes from Gram-positive bacterial cell membrane damage. Tests on cell culture toxicity and host component safety showed promise. Novel diarylurea compounds show promise as Gram-positive antimicrobials. These compounds offer prospects for study and optimization.
OBJECTIVE: The rise of antibiotic resistance among bacterial pathogens poses a significant threat to global health, underscoring the urgent need for novel antimicrobial agents. This study presents research on a promising class of novel compounds with potent antibacterial properties against Gram-positive bacteria, notably Staphylococcus aureus and MRSA. What sets these novel analogs apart is their superior efficacy at substantially lower concentrations compared with commonly used antibiotics like ciprofloxacin and gentamycin. Importantly, these compounds act by disrupting the bacterial cell membrane, offering a unique mechanism that could potentially circumvent existing resistance mechanisms. Preliminary safety assessments also highlight their potential for therapeutic use. This study not only opens new avenues for combating antibiotic-resistant infections but also underscores the importance of innovative chemical approaches in addressing the global antimicrobial resistance crisis.
OBJECTIVE: The rise of antibiotic resistance among bacterial pathogens poses a significant threat to global health, underscoring the urgent need for novel antimicrobial agents. This study presents research on a promising class of novel compounds with potent antibacterial properties against Gram-positive bacteria, notably Staphylococcus aureus and MRSA. What sets these novel analogs apart is their superior efficacy at substantially lower concentrations compared with commonly used antibiotics like ciprofloxacin and gentamycin. Importantly, these compounds act by disrupting the bacterial cell membrane, offering a unique mechanism that could potentially circumvent existing resistance mechanisms. Preliminary safety assessments also highlight their potential for therapeutic use. This study not only opens new avenues for combating antibiotic-resistant infections but also underscores the importance of innovative chemical approaches in addressing the global antimicrobial resistance crisis.
摘要：
需要新型抗微生物剂来对抗抗微生物抗性。这项研究测试了新型的含五氟硫烷基的三氯卡班类似物的潜在抗菌功效。使用标准程序生产含五氟硫烷基的三氯卡班类似物。测试了20种新化合物对7种革兰氏阳性和革兰氏阴性指示菌株以及10种临床分离株的抗菌和抗生物膜活性。机制研究集中在细胞膜损伤上，氧化还原硫醇，铁硫簇，和氧化应激来解释化合物的活性。使用真核细胞系中的细胞毒性实验评估安全性概况。筛选后,与环丙沙星和庆大霉素相比，所选成分在较低浓度下对革兰氏阳性细菌具有更好的抗菌和抗生物膜活性。例如,一种化合物的最小抑制浓度<0.0003mM，但环丙沙星有0.08mM。机理研究表明，这些新型化合物不会影响硫醇含量的降低，铁硫簇，或过氧化氢途径。它们的影响来自革兰氏阳性细菌细胞膜损伤。对细胞培养毒性和宿主成分安全性的测试显示出希望。新型二芳基脲化合物显示出有望作为革兰氏阳性抗菌剂。这些化合物为研究和优化提供了前景。
目的：细菌病原体中抗生素耐药性的上升对全球健康构成了重大威胁，强调了对新型抗菌剂的迫切需要。这项研究提出了对一类有前途的新型化合物的研究，这些化合物具有针对革兰氏阳性细菌的有效抗菌性能，尤其是金黄色葡萄球菌和MRSA。使这些新的类似物与众不同的是,与常用的抗生素如环丙沙星和庆大霉素相比,它们在显著更低的浓度下具有优异的功效。重要的是,这些化合物通过破坏细菌细胞膜起作用，提供了一种独特的机制，可以潜在地规避现有的抵抗机制。初步安全性评估也突出了其治疗用途的潜力。这项研究不仅为对抗抗生素耐药性感染开辟了新的途径，而且强调了创新化学方法在解决全球抗生素耐药性危机中的重要性。
目的：细菌病原体中抗生素耐药性的上升对全球健康构成了重大威胁，强调了对新型抗菌剂的迫切需要。这项研究提出了对一类有前途的新型化合物的研究，这些化合物具有针对革兰氏阳性细菌的有效抗菌性能，尤其是金黄色葡萄球菌和MRSA。使这些新的类似物与众不同的是,与常用的抗生素如环丙沙星和庆大霉素相比,它们在显著更低的浓度下具有优异的功效。重要的是,这些化合物通过破坏细菌细胞膜起作用，提供了一种独特的机制，可以潜在地规避现有的抵抗机制。初步安全性评估也突出了其治疗用途的潜力。这项研究不仅为对抗抗生素耐药性感染开辟了新的途径，而且强调了创新化学方法在解决全球抗生素耐药性危机中的重要性。
