硫相关的1,2,4-三醇:合成,结构见解和抗菌和化疗资料
Nada A El-Emam1, Mahmoud B El-Ashmawy1, Ahmed A B Mohamed1
1Department of Medicinal Chemistry, Faculty of Pharmacy, Mansoura University, Mansoura 35516, Egypt.
Pharmaceuticals (Basel, Switzerland)
|September 28, 2024
概括
合成了新的三二衍生物,并对它们的生物活性进行了评估. 这些化合物表现出显著的抗菌和抗增殖作用,其中一些针对DNA回旋酶和循环素依赖激酶2.
科学领域:
- 药用化学 医学化学
- 有机合成 有机合成
- 药理学 药理学 是一个学科.
背景情况:
- 烯衍生物和1,2,4-triazole-3-thiones是众所周知的各种生物活动.
- 探索新型异环化合物对于药物发现至关重要.
研究的目的:
- 为了合成新型的4-haloaryl-5-(thiophen-2-yl/5-bromothiophen-2-yl)-2,4-dihydro-3H-1,2,4-triazole-3-thiones及其2-aminomethyl衍生物.
- 评估合成化合物的体外抗微生物和抗增殖活性.
- 研究结构-活动关系和分子机制.
主要方法:
- 通过二甲基二碳水化合物与甲基异硫酸酸盐的反应合成三甲基二甲基的核心结构.
- 进一步衍生以获得2 - 氨基甲基替代的三醇 - .
- 对抗细菌和真菌菌株的抗微生物活性体外评估.
- 针对HepG-2和MCF-7癌细胞系的体外抗增殖试验.
- 单晶X射线衍射用于结构分析.
- 对DNA回旋酶和CDK2.2进行分子对接研究.
主要成果:
- 成功合成了新型的三醇-氨酸衍生物 (化合物5a-e和6a-10b).
- 化合物5a-e,6a-e,7a-d,8,9,10a和10b表现出明显的抗菌活性,对抗阳性和阴性细菌 (例如大肠杆菌).
- 化合物5e,6a-e,7a-d和10a对HepG-2和MCF-7癌细胞系 (IC50<25μM) 显示出强大的抗增殖活性.
- 分子对接表明对DNA回旋酶 (抗菌活性) 和CDK2 (抗增殖活性) 的高度亲和力.
结论:
- 合成的三二衍生物具有有前途的抗菌和抗增殖特性.
- 这些化合物的活性与它们的结构特征和与关键生物标 (如DNA旋转酶和CDK2) 的潜在相互作用有关.
- 这些新型化合物代表了开发新抗微生物和抗癌剂的潜在线索.
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