双作用β-aminothiochromones:设计,合成和评估作为抗微生物和抗血管原剂
M S Ajay Krishna1, K T Ashitha1, Meghashyama Prabhakara Bhat2
1Chemical Sciences and Technology Division, CSIR-National Institute for Interdisciplinary Science and Technology (NIIST), Thiruvananthapuram 695019, Kerala, India; Academy of Scientific and Innovative Research (AcSIR), Ghaziabad 201002, India.
Bioorganic & medicinal chemistry letters
|February 19, 2025
概括
新型β-aminothiochromone化合物被合成用于对抗多药耐药细菌. 有前途的候选药物3m和3ae显示出显著的抗微生物和抗血管原作用,为新药发现提供了潜力.
科学领域:
- 药用化学 医学化学
- 药物发现 药物发现 药物发现
- 有机合成 有机合成
背景情况:
- 新兴的抗菌素耐药性需要开发新的治疗药物.
- 多药耐药 (MDR) 细菌对全球健康构成重大威胁.
- 提奥克罗蒙衍生物在各种生物活动中表现出潜力.
研究的目的:
- 设计和合成新的β-aminothiochromone衍生物.
- 评估合成的化合物对MDR细菌和真菌菌株的抗菌活性.
- 调查有前途的化合物的抗血管性质和内结合相互作用.
主要方法:
- 通过阿齐里丁环开放合成β-aminothiochromones.
- 使用光谱,分析和X射线晶体学进行结构性表征.
- 在体外对抗微生物测试对抗阳性,阴性细菌和真菌.
- 在HepG2细胞上的体外抗血管生成测定.
- 在基分子对接研究中对抗DNA旋转酶和Topoisomerase IV.
主要成果:
- 一系列β-aminothiochromone化合物 [3a-m) 和 3a-a-o) ]被成功合成和表征.
- 所有化合物都表现出中度的体外抗菌活性,其中3m和3ae化合物显示出更高的疗效.
- 化合物3m和3ae表现出显著的抗血管性质.
- 在体研究表明,3m和3ae与目标蛋白DNA旋转酶和Topoisomerase IV具有有利的结合能.
结论:
- 合成的β-aminothiochromone衍生物代表了开发新抗菌剂的有希望的支架.
- 化合物3m和3ae显示出进一步开发的潜力,作为具有抗微生物和抗血管原性活动的双重作用剂.
- 这些发现支持对β-aminothiochromones的探索,以应对耐药微生物和血管生成相关疾病所带来的挑战.
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