新型双子四级化合物的合成和广泛的生物杀伤作用
Natalie Zivna1, Michaela Hympanova2, Rafael Dolezal2
1Department of Toxicology and Military Pharmacy, Military Faculty of Medicine, University of Defence, Trebesska 1575, 500 05 Hradec Kralove, Czech Republic; Biomedical Research Centre, University Hospital Hradec Kralove, Sokolska 581, 500 05 Hradec Kralove, Czech Republic.
Bioorganic chemistry
|July 20, 2024
概括
新型双子四元化合物 (QACs) 显示出广泛的抗微生物,抗真菌和杀毒活性. 化合物12提供了一个有希望的,较少的细胞毒性替代现有消毒剂对抗耐药细菌.
科学领域:
- 药用化学 医学化学
- 抗微生物耐药性 抗微生物耐药性
- 生物化学 生物化学
背景情况:
- 滥用抗生素驱动细菌对抗生素和消毒剂的耐药性,如四级化合物 (QAC).
- 双子座QAC,一种具有双极头的新型类型,显示出潜力.
- 双子QAC的octenidine (OCT) 是有效的,但具有可溶性和细胞毒性问题.
研究的目的:
- 开发新型的奥氏胺 (OCT) 衍生物.
- 评估它们的抗微生物,抗真菌和杀病毒性质.
- 为了识别具有提高疗效和降低细胞毒性的化合物.
主要方法:
- 在片选用于膜透预测.
- 针对格拉姆阳性和格拉姆阴性细菌菌株和生物膜的抗菌检测.
- 细胞毒性和抗真菌测定.
- 对特定病毒进行杀毒活性测试.
主要成果:
- 大多数衍生药物显示对高阳性细菌具有很高的疗效.
- 化合物7,8,10-12对克拉姆阴性细菌有效.
- 组合6-8优于OCT和BAC标准的性能.
- 化合物12表现出广泛的活性,低细胞毒性和抗真菌作用.
- 化合物1显示出高的真菌选择性和有效性.
- 化合物4,6,8,9,10和12表现出杀病毒活性.
结论:
- 新型双子QAC提供了增强的抗微生物,抗真菌和杀毒性质.
- 化合物12是一种有前途的替代消毒剂,具有广泛的活性和低细胞毒性.
- 这些化合物解决了微生物对当前药物耐药性的挑战.
相关概念视频
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Direct alkylation is not a suitable method for synthesizing amines because it produces polyalkylated products. Gabriel synthesis is the most preferred method to exclusively make primary amines. The method uses phthalimide, which contains a protected form of nitrogen that participates in alkylation only once to predominantly give primary amines.
Strong bases like NaOH or KOH deprotonate the phthalimide to form the corresponding anion, which acts as a nucleophile. Further, the anion attacks an...
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01:30Preparation of Amines: Alkylation of Ammonia and Amines
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Each alkylation step makes the nitrogen center more nucleophilic, which triggers successive alkylations until a quaternary ammonium salt is formed. Considering...
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01:26Physical Properties of Amines
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