合成,表征,抗糖化评价,分子对接和ADMET研究的4-thiazolidinone衍生物的合成,表征,抗糖化评价,分子对接和ADMET研究
Ashanul Haque1,2, Mohd Wajid Ali Khan1,2, Khalaf M Alenezi1,2
1Department of Chemistry, College of Science, University of Ha'il, Ha'il 81451, Saudi Arabia.
ACS omega
|January 15, 2024
概括
新的4-thiazolidinone化合物进行了合成和测试,以抑制糖化. 化合物3有效抑制了糖化,并逆转了高血糖引起的蛋白质结构变化,显示出作为治疗剂的潜力.
科学领域:
- 药用化学 医学化学
- 有机合成 有机合成
- 生物化学 生物化学
背景情况:
- 小分子糖化抑制剂对于治疗糖尿病,心血管和神经退行性疾病等慢性疾病至关重要.
- 先进的糖化终产品 (AGEs) 有助于疾病的发病.
- 4- thiazolidinone衍生物被认为具有抑制 AGE 形成的潜力.
研究的目的:
- 为了合成和描述新型的5-arylidene 3-cyclopropyl-2-(phenylimino) thiazolidin-4-one化合物.
- 为了评估这些化合物对人类血清白糖化的抑制活性.
- 研究这些化合物的潜力,作为治疗糖化相关疾病的治疗剂.
主要方法:
- 四种新的4-thiazolidinone衍生物的合成和表征.
- 在实验室中对人类血清中阿尔伯明糖化抑制的评估.
- 计算研究包括分子对接,ADME/Tox和密度函数理论 (DFT).
主要成果:
- 化合物3,5-(2H-1,3-二醇-5-ylmethylidene) -3-cyclopropyl-2-(phenylimino) -1,3-thiazolidin-4-one,已经证明了强大的抑制糖化.
- 化合物3逆转了由高血糖引起的人类血清白蛋白的构造变化 (α-螺旋和β-片).
- 计算分析表明合成化合物具有良好的药物相似性,安全性和稳定性,其中化合物1显示了最高的对接得分.
结论:
- 合成的4-thiazolidinone衍生物,特别是化合物3,显示出作为糖化抑制剂的显著潜力.
- 化合物3有效地减轻了糖化对蛋白质结构的有害影响.
- 这项研究为开发针对慢性疾病的新型治疗策略提供了对4-thiazolidinones的生物活性有价值的见解.
相关概念视频
01:23Dipeptidyl Peptidase 4 Inhibitors
188
Dipeptidyl peptidase 4 (DPP-4) is a serine protease widely distributed in the body. It's involved in the inactivation of GLP-1 and GIP hormones, which are crucial for insulin regulation. DPP-4 inhibitors, such as sitagliptin (Januvia), saxagliptin (Onglyza), linagliptin (Tradjenta), alogliptin (Nesina), and vildagliptin (Galvus), help increase the proportion of active GLP-1, enhancing insulin secretion. These inhibitors work by competitively binding to DPP-4. This binding causes a...
188
01:28Structure-Activity Relationships and Drug Design
726
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...
726
01:26Drug 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
01:15Antihypertensive Drugs: Thiazide-Class Diuretics
643
Thiazide diuretics are sulfonamide derivatives featuring a benzothiadiazine ring system in their molecular structure. Based on this structure, thiazide diuretics can be categorized into two groups: thiazide-type and thiazide-like diuretics. Thiazide-type diuretics, including hydrochlorothiazide and chlorothiazide, consist of a benzothiadiazine backbone with an attached sulfonamide group. Thiazide-like diuretics, such as chlorthalidone and indapamide, lack the thiazide ring but demonstrate...
643