一种来自Allostreptomyces RD068384的新型多环四甲基麦克罗拉克坦:立体化学和抗真菌潜力
Marwa Elsbaey1,2, Yuki Samaru3, Engy Elekhnawy4
1Pharmacognosy Department, Faculty of Pharmacy, Mansoura University, Mansoura, 35516, Egypt. marwaelsebay1611@mans.edu.eg.
The Journal of antibiotics
|April 9, 2024
概括
一种新型化合物,亚洛斯特胺及其类型显示抗真菌活性对抗白菌. 化合物3还通过降低关键基因的调节来抑制生物膜的形成,这表明它有可能作为一种抗真菌疗法.
科学领域:
- 自然产品化学 自然产品化学
- 微生物学 微生物学
- 分子生物学分子生物学
背景情况:
- 虫 Candida albicans 感染构成重大威胁,需要新的治疗策略.
- 抗真菌药物耐药性和生物膜形成使治疗结果复杂化.
- 从微生物来源寻找新的抗菌剂的研究正在进行中.
研究的目的:
- 从Allostreptomyces RD068384.4中分离和描述新的化合物.
- 评估分离化合物的抗真菌和抗菌膜活动,以对抗白 Candida albicans.
- 调查化合物3的抗菌膜活性背后的分子机制.
主要方法:
- 使用NMR,MS,ROESY和ECD分析对化合物的分离和结构阐明.
- 对多个Candida albicans分离物进行抗真菌敏感性测试 (MIC确定).
- 生物膜抑制试验和定量实时PCR (qRT-PCR) 来评估基因表达.
主要成果:
- 一种新型的多环四甲基麦克罗拉克坦,allostreptamide (1),与四种已知的化合物一起被分离出来.
- 所有分离的化合物都对Candida albicans表现出抗真菌活性,MIC范围为64至2048μg/mL.
- 化合物3表现出显著的抗菌膜活性,降低成熟生物膜的活力,并降低生物膜相关基因 (BCR1,PLB2,ALS1,SAP5) 的调节.
结论:
- 阿洛斯特胺和它的同类物质具有抗性质,可以对抗Candida albicans.
- 化合物3表现出有前途的抗生素膜活性,为对抗Candida albicans感染提供了潜在的治疗途径.
- 化合物3对特定毒性基因的下调提供了对其抗菌膜效应的机械洞察力.
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