设计,合成,DFT,对接研究,以及含有硫胺基衍生物的新型本齐米达的抗菌评估
Kajal Singh1, Vishal K Singh2, Richa Mishra3
1Photophysical and Therapeutic Laboratory, Department of Chemistry, C.M.P. Degree College (A constituent P.G. College of University of Allahabad), Prayagraj 211002, India.
Bioorganic chemistry
|May 31, 2024
概括
新的含芝醇的硫胺显示出强大的抗菌活性对抗细菌和真菌. 这些使用in silico方法设计的化合物表现出显著的抑制和协同效应,具有针对多药耐药菌株的潜力.
科学领域:
- 药用化学 医学化学
- 计算化学的计算化学
- 微生物学 微生物学
背景情况:
- 含有西米达的硫胺被探索为抗菌性质.
- 在形设计和新衍生物的合成对于药物发现至关重要.
研究的目的:
- 设计,合成和评估新型的胺-硫胺衍生物作为抗菌剂.
- 研究这些化合物的抗菌和抗真菌活性.
- 通过酶抑制和结构-活性关系研究来阐明作用机制.
主要方法:
- 在形设计和合成本齐米达-硫胺衍生物.
- 苏微稀释方法用于抗菌查,对抗阳性和阴性细菌.
- 使用分数抑制度 (FIC) 与参考药物进行的组合研究.
- 酶抑制测定针对基转移酶和二二酸合成酶.
- 使用食物中毒方法进行抗真菌查.
- 结构活动关系 (SAR) 分析和分子对接.
主要成果:
- 合成的化合物显示出显著的抗菌活性,最小抑制度 (MIC) 值在100-1.56μg/mL之间.
- 组合分析显示了强大的抑制效率,一些化合物比现有药物具有同等或更强的效力.
- 当与氨基醇和硫甲醇结合使用时,观察到协同效应.
- 化合物3显示出对基转移酶和二甲酸合成酶的良好抑制.
- 抗真菌查确定了对致病性真菌物种有潜在作用的化合物.
- SAR分析表明,脂性替代剂有利于抗菌活性,而水性替代剂有利于抗真菌活性.
结论:
- 设计的胺-硫胺衍生物具有有前途的抗微生物和抗真菌活性.
- 这些化合物具有作为对抗多药耐药 (MDR) 微生物菌株的治疗剂的潜力.
- 在 silico 和 in vitro 结果显示出强烈的连贯性,验证了设计和评估方法.
相关概念视频
Structure-Activity Relationships and Drug Design
699
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...
699
Amines to Sulfonamides: The Hinsberg Test
3.4K
The Hinsberg test is a method to identify primary, secondary and tertiary amines, named after its pioneer, Oscar Hinsberg. Here, amines are treated with benzenesulfonyl chloride, also known as the Hinsberg reagent, in the presence of an excess of aqueous base, followed by acidification. Based on the nature of the amines, different changes are observed.
Generally, a primary amine reacts with the Hinsberg reagent to produce an N-substituted benzenesulfonamide. The electron-withdrawing...
Generally, a primary amine reacts with the Hinsberg reagent to produce an N-substituted benzenesulfonamide. The electron-withdrawing...
3.4K
Electrophilic Aromatic Substitution: Sulfonation of Benzene
6.0K
Sulfonation of benzene is a reaction wherein benzene is treated with fuming sulfuric acid at room temperature to produce benzenesulfonic acid. Fuming sulfuric acid is a mixture of sulfur trioxide and concentrated sulfuric acid.
6.0K
Drug Discovery: Overview
7.8K
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...
7.8K
Combined Effects of Drugs: Synergism
3.8K
Synergism is a useful mechanism where combining two or more drugs is more effective than each constituent used alone. Such combinations are also called supra-additive interactions. The drugs collectively enhance the final therapeutic effect by acting on different targets. Another advantage is that the low dose of each constituent drug is sufficient to achieve the desired effect. This helps reduce the duration of therapy and lower the adverse effects of these drugs.
Such synergistic combinations...
Such synergistic combinations...
3.8K
Directing and Steric Effects in Disubstituted Benzene Derivatives
3.0K
When disubstituted benzenes undergo electrophilic substitution, the product distribution depends on the directing effect of both substituents. When the directing effects of both substituents reinforce each other, a single product is obtained. For example, bromination of p-nitrotoluene occurs ortho to the methyl group and meta to the nitro group, which is the same position, resulting in a single product. However, if the directing effects of the two groups oppose each other, the...
3.0K


