设计,合成,评估和优化新型醇类似物作为强效抗真菌剂
Juan Zhang1, Zhen Wang1, Conghao Gai2
1School of Pharmacy, Second Military Medical University, Shanghai 200433, China; School of Pharmacy, Key Laboratory of Molecular Pharmacology and Drug Evaluation (Yantai University), Ministry of Education, Collaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs in Universities of Shandong, Yantai University, Yantai 264005, China.
Bioorganic & medicinal chemistry
|December 10, 2023
概括
新的醇类比物被开发为潜在的抗真菌药物. 几种化合物表现出广泛的活性,其中一些显示出对Candida albicans菌株和低毒性的良好疗效.
科学领域:
- 药用化学 医学化学
- 药理学 药理学是指药理学的学科.
- 菌类学 菌类学是指菌类学.
背景情况:
- 醇化合物对于抗真菌药物开发至关重要.
- 之前的研究为新型模拟合成提供了基础.
- 新兴的抗真菌耐药性需要新的治疗药物.
研究的目的:
- 设计和合成用于抗真菌药物开发的新型醇类似物.
- 评估这些新化合物的广泛抗真菌活性.
- 调查结构-活动关系和潜在的作用机制.
主要方法:
- 新型醇类似物的化学合成.
- 对各种真菌菌株进行抗真菌活性查,包括耐药的真菌菌株.
- 最低抑制度 (MIC80) 的确定.
- 对NIH/3T3细胞的细胞毒性评估.
- 结构-活性关系 (SAR) 分析和分子对接研究.
主要成果:
- 大多数合成的醇类比物都表现出广泛的抗真菌活性.
- 化合物B3,B7,B8,B11,B12和E9对Candida albicans菌株表现出强烈的活性 (MIC80:0.0156个单位/毫升).
- 化合物B3对具有较低对哺乳动物细胞毒性的抗可纳耐药Candida albicans菌株表现出显著的活性.
- SAR和对接研究表明,2--4-基和1,2,3-triazole部分增强了抗真菌性质.
结论:
- 新型醇类比物显示出作为潜在的抗真菌药物候选者的希望.
- 化合物B3是一个特别强大的候选者,因为它对抗耐药菌株的有效性和有利的安全性.
- 已识别的结构特征是增强抗真菌活性的关键,可能是通过酶相互作用.
相关概念视频
Drug Discovery: Overview
7.9K
Drug discovery is a multifaceted process involving extensive screening, testing, and optimization of lead compounds to identify potential new drugs for therapeutic use. It combines several approaches, including screening large numbers of natural products, chemical modification of known active molecules, identification of new drug targets, and rational design based on biological mechanisms and drug-receptor structure. These approaches are carried out in both academic research laboratories and...
7.9K
Aryldiazonium Salts to Azo Dyes: Diazo Coupling
2.9K
The reaction of weakly electrophilic aryldiazonium (also called arenediazonium) salts with highly activated aromatic compounds leads to the formation of products with an —N=N— link, called an azo linkage. This reaction, presented in Figure 1, is known as diazo coupling and occurs without the loss of the nitrogen atoms of the aryldiazonium salt. Highly activated aromatic compounds such as phenols or arylamines favor the diazo coupling reaction. The coupling generally occurs at the...
2.9K
Structure-Activity Relationships and Drug Design
728
Drug design is a dynamic field that involves discovering and developing new medications based on specific biological targets. This process heavily relies on structure-activity relationships (SAR) and quantitative structure-activity relationships (QSAR) to guide the design and optimization of efficient drugs.
SAR studies the intricate relationship between a drug's chemical structure and biological activity. It focuses on understanding how modifications to a drug's structure can influence...
SAR studies the intricate relationship between a drug's chemical structure and biological activity. It focuses on understanding how modifications to a drug's structure can influence...
728
Preparation of 1° Amines: Azide Synthesis
3.9K
Direct alkylation of ammonia produces polyalkylated amines, along with a quaternary ammonium salt. To exclusively prepare primary amines, the azide synthesis method can be used.
Azide ions act as good nucleophiles and react with unhindered alkyl halides to form alkyl azides. Alkyl azides do not participate in further nucleophilic substitution reactions, thereby eliminating the chances of polyalkylated products. Alkyl azides are reduced by hydride-based reducing agents, like lithium aluminum...
Azide ions act as good nucleophiles and react with unhindered alkyl halides to form alkyl azides. Alkyl azides do not participate in further nucleophilic substitution reactions, thereby eliminating the chances of polyalkylated products. Alkyl azides are reduced by hydride-based reducing agents, like lithium aluminum...
3.9K


