循环硫基碳酸盐在提促进路径中独立释放碳酸和硫化
Yu Zhao1, Andrea K Steiger1, Michael D Pluth1
1Department of Chemistry and Biochemistry, Institute of Molecular Biology, Materials Science Institute , University of Oregon , Eugene , Oregon 97403 , United States.
Journal of the American Chemical Society
|August 3, 2019
概括
新的硫基碳酸盐 (SulfenylTCMs) 通过定义的途径有效释放硫化 (H2S). 这些H2S供体,包括像YZ-597这样的NSAID混合体,为开发新型治疗药物提供了有希望的平台.
科学领域:
- 生物化学
- 医学化学
- 药理学
背景情况:
- 硫化 (H2S) 在各种生理和病理条件下起着保护作用的关键信号分子.
- 胺是已知的H2S捐赠体,通常与非类固醇抗炎药物 (NSAIDs) 结合,产生有毒性降低的混合体,尽管它们的H2S释放机制尚未完全理解.
研究的目的:
- 合成和评估一种新的H2S捐赠体,即硫基碳酸盐 (SulfenylTCMs).
- 阐明这些新化合物的H2S释放机制.
- 为潜在的治疗应用开发和评估H2S-NSAID混合体.
主要方法:
- 硫基酸衍生物的合成
- 使用细胞试验评估H2S释放效率
- 确定H2S释放通路的机制研究,包括二醇激活和碳酸 (COS) 转化.
- 将硫基酸盐部分与NSAID结合,以纳为例,以创建混合分子.
主要成果:
- 合成了硫TCM,并证明了有效的H2S释放 (高达90%).
- 细胞醇激活硫TCM,释放碳硫化物 (COS),然后通过碳酸无水酶 (CA) 转化为H2S.
- 还确定了独立于COS的H2S释放途径.
- 硫基酸盐组成功与NSAID结合,产生YZ-597,在细胞环境中有效释放H2S.
结论:
- 硫基碳酸盐是一种具有明确释放机制的新型有效H2S供体.
- 这些化合物为开发新型H2S释放剂提供了多功能平台,包括具有潜在治疗益处的H2S-NSAID杂交物.
- 通过不同的途径调整H2S释放的能力提高了它们在生物医学研究和药物开发中的实用性.
相关概念视频
Structure and Nomenclature of Thiols and Sulfides
5.7K
Thiols and sulfides are sulfur analogs of alcohols and ethers, respectively, where the sulfur atom takes the place of the oxygen atom. Thus, thiols are generally represented as RSH, where R is an alkyl substituent and —SH is the functional group. On the other hand, in sulfides, the central sulfur atom is bonded to two hydrocarbon groups on either side. Depending upon the type of group, sulfides can be either symmetrical or asymmetrical. Both thiols and sulfides display a bent geometry,...
5.7K
Preparation and Reactions of Sulfides
5.7K
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.
5.7K
Hydrogen Bonds
131.5K
Hydrogen bonds are weak attractions between atoms that have formed other chemical bonds. One of these atoms is electronegative, like oxygen, and has a partial negative charge. The other is a hydrogen atom that has bonded with another electronegative atom and has a partial positive charge.
Hydrogen Bonds Control the World!
Because hydrogen has very weak electronegativity when it binds with a strongly electronegative atom, such as oxygen or nitrogen, electrons in the bond are unequally shared....
Hydrogen Bonds Control the World!
Because hydrogen has very weak electronegativity when it binds with a strongly electronegative atom, such as oxygen or nitrogen, electrons in the bond are unequally shared....
131.5K
Preparation and Reactions of Thiols
7.5K
Thiols are prepared using the hydrosulfide anion as a nucleophile in a nucleophilic substitution reaction with alkyl halides. For instance, bromobutane reacts with sodium hydrosulfide to give butanethiol.
7.5K
Introduction to Test of Independence
2.9K
In statistics, the term independence means that one can directly obtain the probability of any event involving both variables by multiplying their individual probabilities. Tests of independence are chi-square tests involving the use of a contingency table of observed (data) values.
The test statistic for a test of independence is similar to that of a goodness-of-fit test:
The test statistic for a test of independence is similar to that of a goodness-of-fit test:
2.9K
Hypothesis Test for Test of Independence
7.4K
The test of independence is a chi-square-based test used to determine whether two variables or factors are independent or dependent. This hypothesis test is used to examine the independence of the variables. One can construct two qualitative survey questions or experiments based on the variables in a contingency table. The goal is to see if the two variables are unrelated (independent) or related (dependent). The null and alternative hypotheses for this test are:
H0: The two variables (factors)...
H0: The two variables (factors)...
7.4K


