合成,生物和分子对接研究的亚-亚衍生物作为潜在的抗结核剂
Samin A Shaikh1, Shivaji R Labhade2, Raju R Kale2
1Department of Chemistry, Kr. V. N. Naik Shikshan Prasarak Sanstha's Arts, Commerce and Science College, Canada Corner, 422002, Nashik, Maharashtra, India.
Chemistry & biodiversity
|May 3, 2024
概括
新的亚二醇结合的亚二醇衍生物显示出作为抗结核病剂的前景. 化合物5l对Mycobacterium tuberculosis表现出强烈的活性,并与ThyX酶发现了潜在的相互作用.
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:
- 结核病 (TB) 构成了重大的全球卫生挑战,感染率和死亡率不断上升.
- 现有的抗结核病药物面临局限性,需要开发新型治疗剂.
- thiazole 和 thiadiazole 支架以其多样化的生物活动而闻名.
研究的目的:
- 为了合成和评估新型的亚二醇相关的亚二醇衍生物的抗结核活性.
- 为了识别具有针对Mycobacterium tuberculosis的强有力的活性的化合物.
- 使用in silico方法调查潜在的药物标和分子相互作用.
主要方法:
- 合成十二种提亚-提亚醇衍生物 (化合物5a-5l).
- 使用光谱技术进行结构性表征.
- 通过最小抑制度 (MIC) 试验评估抗结核活性.
- 在基分析中,包括对结核病的ThyX酶进行药测绘和分子对接.
主要成果:
- 化合物5g,5i和5l表现出显著的抗结核活性.
- 化合物5l表现出最强烈的活性,MIC值为7.1285μg/ml,对抗M.结核病.
- 在 silico 研究中,结核 ThyX 被确定为潜在的目标,在化合物和酶残留物之间观察到关键相互作用 (Arg95,Cys43,His69,Arg87).
结论:
- 与提亚醇相关的提亚醇衍生物是开发抗结核病药物的一类有前途的化合物.
- 化合物5l是进一步研究的潜在主要候选物.
- 确定了与ThyX的相互作用,提供了对作用机制的洞察力,并指导了未来的药物设计.
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