合成的 Bis-Triphenyl Phosphonium 基纳米囊泡对几种临床相关的超级细菌具有强大和选择性的抗菌作用
Silvana Alfei1, Guendalina Zuccari1,2, Francesca Bacchetti1
1Department of Pharmacy, University of Genoa, Viale Cembrano, 16148 Genoa, Italy.
Nanomaterials (Basel, Switzerland)
|August 28, 2024
概括
新的盐具有强大的抗菌活性,可以对抗多药耐药 (MDR) 病原体. 这种新型化合物BPPB显示出对具有挑战性的格兰正和格兰阴性细菌,包括ESKAPE病原体的广泛疗效.
科学领域:
- 药用化学 医学化学
- 抗菌剂 抗菌剂 抗菌剂
- 纳米技术纳米技术
背景情况:
- 越来越多的抗药性 (MDR) 病原体需要新的抗菌战略.
- 四级盐 (QPSs) 显示出抗菌潜力,但比四级盐 (QASs) 更少研究.
- 之前的研究表明,三盐对MDR阳性细菌具有细菌静止和细胞毒性作用.
研究的目的:
- 合成和评估一种新型的,水溶性,硬质阻四级盐 (BPPB),用于广泛的抗菌活性.
- 研究BPPB的自我组装特性和物理化学特性.
- 评估BPPB对临床相关的MDR病原体的抗菌疗效和细胞毒性.
主要方法:
- 合成BPPB,一个具有两个三基基团的球-两分子.
- 使用光谱技术 (ATR-FTIR,NMR,UV),质谱法 (FIA-MS),元素分析和电位计定位进行表征.
- 使用DLS和光学显微镜评估自我组装 (囊泡形成),并测量泽塔电位.
- 对50种临床分离的格拉姆阳性和格拉姆阴性细菌的最小抑制度 (MIC) 的确定.
- 对HepG2 (人类肝脏) 和Cos-7 (子脏) 细胞系的细胞毒性评估.
主要成果:
- 在稀释溶液中,BPPB自组装成45纳米球状囊泡,表现出正的泽塔电位 (+18 mV).
- 对所有测试的临床分离物,包括ESKAPE病原体,观察到出色的广泛抗菌活性.
- MIC值在0.250微克/毫升至32微克/毫升之间,其中对抗MDR抗最后抗生素 (胆固醇,碳烯, cefiderocol) 耐药的格拉姆阴性细菌的最高值.
- BPPB表现出有利的选择性指数 (>10) 对格拉姆阳性细菌和关键的格拉姆阴性病原体,如大肠杆菌.
结论:
- 合成的博拉-两性盐,BPPB,表现出强大的广泛抗菌活性.
- BPPB显示出对高耐药性格拉姆阴性细菌的有希望的有效性,解决了严重的未满足的医疗需求.
- 良好的安全性和强大的活性使BPPB成为进一步临床开发作为新型抗菌剂的有希望的候选人.
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