合成和生物评估硫烯酸衍生物作为潜在的抗克拉米迪亚药物
Jiachen Feng1, Luana Janaína de Campos1, Mohamed A Seleem1
1Department of Pharmaceutical Sciences, College of Pharmacy, University of Nebraska Medical Center, Omaha, NE 68198-6125, United States.
Bioorganic & medicinal chemistry
|July 15, 2023
概括
新的硫烯酸化合物显示出作为选择性治疗克拉米迪亚螺旋虫感染的有希望的可能性. 这些候选药物有效抑制细菌生长,并表现出良好的安全性,因此需要进一步开发.
科学领域:
- 药用化学 医学化学
- 微生物学 微生物学
- 药物发现 药物发现 药物发现
背景情况:
- 克拉米迪亚性状菌是全球性传播细菌感染的主要原因之一.
- 未经治疗的感染会导致严重的健康问题,包括失明和生殖损伤.
- 目前,没有专门批准用于治疗克拉米迪亚的药物.
研究的目的:
- 开发具有抗甲基胺活性的新型硫烯酸衍生物.
- 为了评估新的对抗Chlamydia trachomatis的同类药物的疗效和选择性.
- 研究化合物的作用机制和安全概况.
主要方法:
- 新型硫烯酸衍生物的合成和表征.
- 在体外测试针对C. trachomatis的抗克拉米迪活性.
- 使用 Staphylococcus aureus 和 Escherichia coli 的细菌选择性测定.
- 在的分子对接研究中,准了克拉米迪亚蛋白酶.
- 哺乳动物细胞系和生理流体中的细胞毒性和稳定性评估.
主要成果:
- 新合成的硫胺类类似物显示出显著抑制C. trachomatis生长.
- 与之前的分子相比,化合物22表现出增强的活性.
- 化合物22显示有选择性,没有观察到对S. aureus或E. coli生长的影响.
- 对接研究提供了与目标蛋白酶的结合相互作用的见解.
- 这种化合物表现出良好的细胞毒性概况和生物流体中的稳定性.
结论:
- 硫烯酸代表了一类有前途的选择性抗黑米药物.
- 这些化合物的进一步结构优化对于潜在的治疗应用是有必要的.
- 开发的化合物提供了一个潜在的新策略来对抗克拉米迪亚感染.
相关概念视频
Amines to Sulfonamides: The Hinsberg Test
3.6K
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...
3.6K
Aryldiazonium Salts to Azo Dyes: Diazo Coupling
3.0K
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...
3.0K
Preparation and Reactions of Sulfides
4.9K
Sulfides are the sulfur analog of ethers, just as thiols are the sulfur analog of alcohol. Like ethers, sulfides also consist of two hydrocarbon groups bonded to the central sulfur atom. Depending upon the type of groups present, sulfides can be symmetrical or asymmetrical. Symmetrical sulfides can be prepared via an SN2 reaction between 2 equivalents of an alkyl halide and one equivalent of sodium sulfide.
4.9K
Oral Hypoglycemic Agents: Sulfonylureas
245
Sulfonylureas are oral hypoglycemic agents utilized in treating type 2 diabetes. They are characterized by their unique sulfonylurea chemical structure. The family of sulfonylureas is divided into generations. First-generation sulfonylureas, including tolbutamide (Orinase), chlorpropamide (Diabinese), and tolazamide (Tolinase), trigger insulin release from pancreatic β cells and enhance peripheral tissues' insulin sensitivity. The second-generation members, such as glipizide...
245
Combined Effects of Drugs: Synergism
4.1K
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...
4.1K
Indirect-Acting Cholinergic Agonists: Chemistry and Structure-Activity Relationship
608
Indirect-acting cholinergic agonists are agents that interact with the acetylcholinesterase enzyme in the synaptic cleft, preventing the breakdown of acetylcholine into choline and acetate. Consequently, the concentration of acetylcholine in the synaptic cleft increases. These agonists can be classified into reversible and irreversible inhibitors based on their duration of action.
Reversible inhibitors display short to medium durations of action. Short-acting agents include simple alcohols with...
Reversible inhibitors display short to medium durations of action. Short-acting agents include simple alcohols with...
608


