与三醇连接的pyrazoles功能化的二硫胺具有双重cathepsin B和碳酸无水酶抑制作用
Kiran Siwach1, Priyanka Arya1, Lalit Vats1,2
1Department of Chemistry, Kurukshetra University, Kurukshetra, Haryana, India.
Archiv der Pharmazie
|June 20, 2024
概括
新的二硫胺 - - 皮拉 - - 二醇衍生物被合成为甲素B和碳酸无水酶 (CA) 的双重抑制剂. 这些化合物显示出强大的纳米分子抑制与癌症相关的CA IX和XII,具有有前途的甲素B抑制.
科学领域:
- 药用化学 医学化学
- 酶抑制可以抑制酶.
- 药物发现 药物发现 药物发现
背景情况:
- 碳酸 anhydrase (CA) 和cathepsin B与包括癌症在内的各种疾病有关.
- 开发双重抑制剂提供了一个有前途的治疗策略.
研究的目的:
- 设计和合成与二硫胺相关的新型pyrazole-triazole衍生物.
- 评估它们作为碳酸酶 (CA) 和甲素B的双重抑制剂的潜力.
- 调查结构-活动关系和in silico属性.
主要方法:
- 合成了21种新的1,2,3-三结合的酸,碳酸和碳酸胺.
- 在体外对人类碳酸无水酶 (hCA) 异型I,II,IX,XII和甲素B抑制的酶分析.
- 分子对接研究,以探索酶-抑制剂相互作用.
- 在 silico ADMET 和药物相似性评估.
主要成果:
- 化合物对hCA IX和XII表现出强大的纳米分子抑制,对hCA I比hCA II有选择性.
- 特定的 (16c) 和炭胺 (18b) 衍生物对hCA IX和XII分别显示出高强度.
- 所有合成的化合物都在10−7M时表现出强烈的甲素B抑制,碳胺一般显示出更高的疗效.
- 分子对接和in silico研究提供了关于结合方式和类似药物的特性的见解.
结论:
- 新型二硫胺 - - 皮拉 - - 二醇衍生物是有效的甲素B和碳酸无水酶的双重抑制剂.
- 这些化合物代表了开发针对癌症和其他疾病的新治疗剂的有希望的线索.
- 基于结构-活动关系和in silico数据的进一步优化是有必要的.
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