化氧基核是通过神经毒剂抑制的高效地重新激活胆酶的
Eliska Prchalova1, Rudolf Andrys1, Jaroslav Pejchal2
1University of Hradec Kralove, Faculty of Science, Department of Chemistry, Rokitanskeho 62, 500 03, Hradec Kralove, Czech Republic.
Archives of toxicology
|May 24, 2024
概括
合成了新的化双氧化物,以重新激活抑制的乙胆化酶 (AChE) 和丁胆化酶 (BChE). 一种化合物在活体中显示出有希望的疗效,可以预防大鼠中毒的神经毒剂.
科学领域:
- 药用化学 医学化学
- 神经科学是一个神经科学.
- 毒理学 毒理学 毒理学
背景情况:
- 包括神经毒剂在内的有机化合物抑制了诸如乙胆酶 (AChE) 和丁胆酶 (BChE) 等关键酶.
- 氧化物再激活剂是重要的解毒剂,但开发更有效和更安全的选择仍然是优先事项.
研究的目的:
- 设计和合成具有增强核友性的新型化双氧化物.
- 评估这些新型化合物的体外和体内疗效,作为化ACHE和BCHE的活性化剂.
主要方法:
- 合成了六种新的化双二氧化氧化物.
- 在水溶液和缓冲液中确定pKa值和稳定性.
- 在实验室中对受抑制的ACHE和BCHE进行再激活查.
- 氧化物诱导反应的动态分析.
- 毒和VX中毒大鼠的急性毒性评估和体内测试.
主要成果:
- 合成的氧化物呈现较低的pKa值,与非化类型相比.
- 单氧化物表现出与现有治疗方法相比较的ACHE活性.
- 最有前途的化氧化物表现出良好的中枢神经系统 (CNS) 分布和血液再激活.
- 这种化合物在被VX中毒的老鼠中提供了最佳的保护指数.
结论:
- 新型化双氧化物是抑制胆化酶的有效活性化剂.
- 一种特定的氧化物显示出作为一种活体中神经毒剂毒性抗药物的显著潜力.
- 对这种有前途的化合物进行进一步的研究对于潜在的临床应用是有必要的.
相关概念视频
Anticholinesterase Agents: Poisoning and Treatment
848
Anticholinesterases, also known as cholinesterase inhibitors, work by blocking the breakdown of acetylcholine, leading to its accumulation in the synaptic cleft. This accumulation indirectly enhances both muscarinic and nicotinic actions. These agents are classified as reversible or irreversible based on their mechanism of action.
Irreversible agents form a strong bond with the cholinesterase enzyme, making it inactive. The breakdown of the phosphorylated enzyme is...
Irreversible agents form a strong bond with the cholinesterase enzyme, making it inactive. The breakdown of the phosphorylated enzyme is...
848
Indirect-Acting Cholinergic Agonists: Chemistry and Structure-Activity Relationship
554
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...
554
Indirect-Acting Cholinergic Agonists: Pharmacokinetics
964
Indirect-acting cholinergic agonists, or anticholinesterases, enhance the body's cholinergic activity by inhibiting acetylcholine's breakdown. They are categorized as reversible or irreversible agents based on their mechanism of action. They are further classified into short-acting, intermediate-acting, and long-acting agents based on their duration of action.
Reversible agents containing quaternary amines, such as neostigmine and edrophonium, are not easily absorbed orally because they...
Reversible agents containing quaternary amines, such as neostigmine and edrophonium, are not easily absorbed orally because they...
964
Indirect-Acting Cholinergic Agonists: Mechanism of Action
1.8K
Indirect-acting cholinergic agonists work by interacting with an enzyme called acetylcholinesterase (AChE) in the synaptic cleft. They can be reversible or irreversible inhibitors and have different effects on the enzyme.
Reversible inhibitors like edrophonium bind to a specific part of the enzyme called the anionic catalytic site. They form noncovalent bonds, which means they are not strongly attached to the enzyme. This creates a temporary and less stable enzyme–inhibitor complex,...
Reversible inhibitors like edrophonium bind to a specific part of the enzyme called the anionic catalytic site. They form noncovalent bonds, which means they are not strongly attached to the enzyme. This creates a temporary and less stable enzyme–inhibitor complex,...
1.8K
Indirect-Acting Cholinergic Agonists: Pharmacological Actions
661
Indirect-acting cholinergic agonists, also known as anticholinesterases, exert their pharmacological effects by enhancing cholinergic transmission in various body parts, including the neuromuscular junction, autonomic cholinergic synapses, and the brain.
At the neuromuscular junction, these agents work by inhibiting the breakdown of acetylcholine, allowing it to remain bound to the receptor and bind to nearby receptors. This process leads to repetitive firing of the endplate, causing muscle...
At the neuromuscular junction, these agents work by inhibiting the breakdown of acetylcholine, allowing it to remain bound to the receptor and bind to nearby receptors. This process leads to repetitive firing of the endplate, causing muscle...
661
Direct-Acting Cholinergic Agonists: Pharmacokinetics
1.1K
Direct-acting cholinergic agonists, such as synthetic choline esters and naturally occurring alkaloids, exert their effects by enhancing the actions of acetylcholine and stimulating the parasympathetic nervous system. Synthetic choline esters share structural similarities with acetylcholine. For example, they have a positively charged quaternary ammonium or onium group, contributing to their hydrophilic characteristics. As a result, they are poorly absorbed in the body through oral...
1.1K


