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设计和合成新的以醇为基础的芳酶/iNOS抑制剂,具有亡性抗增殖活性

Lamya H Al-Wahaibi¹, Hesham A Abou-Zied², Mostafa H Abdelrahman³

¹Department of Chemistry, College of Sciences, Princess Nourah Bint Abdulrahman University, Riyadh, Saudi Arabia.

Frontiers in chemistry

|September 23, 2024

概括

新的醇化合物被开发为芳酶和可诱导氧化合成酶 (iNOS) 的双抑制剂,显示出对癌细胞显著的抗增殖活性. 混合体12和16显示出强大的疗效和诱导的亡,表明治疗潜力.

科学领域:

药用化学医学化学
药理学药理学是指药理学的学科.
癌症生物学癌症生物学

背景情况:

芳酶和诱导性氧化合成酶 (iNOS) 是癌症治疗的关键标.
开发双重抑制剂为增强抗癌效果提供了一个有希望的策略.
印醇衍生物已经显示出作为治疗剂的潜力.

研究的目的:

设计,合成和评估作为芳酶和iNOS的双抑制剂的醇衍生物.
评估这些化合物对各种癌症细胞系的抗增殖活性.
为了研究作用机制,包括apoptotic潜力和分子相互作用.

主要方法:

合成醇杂交物 (化合物 3-16).
在体外对抗增殖活性 (GI50值) 的生物评估.
酶抑制测定用于芳酶和iNOS.
亡试验 (酶激活,BCL-2家族蛋白质).
分子对接研究和ADME分析.

主要成果:

合成和评估了3-16种印杂交物.
化合物12和16表现出强大的抗增殖活性,GI50值分别为25nM和28nM.
活跃杂交体 (5,7,12,16) 显示出对芳酶和iNOS的显著抑制.
化合物12和16通过激活caspases-3,8和Bax,并降低Bcl-2的调节来诱导亡.
分子对接证实了与芳酶活性部位的结合相互作用.
根据ADME的特征,可能会降低毒性.

结论:

新型醇衍生物被成功设计和合成为芳酶和iNOS的双抑制剂.
化合物12和16是强大的抗增殖剂,具有有前途的诱导亡能力.
这些发现凸显了这些新型醇杂交体在癌症治疗中的治疗潜力.

关键词:

芳香酶是一种芳香酶.印度尔 (Indole) 是一种制剂.抑制剂抑制剂抑制剂氧化氧化的使用方法皮拉辛 (Pyrazine) 是一种酸盐.合成酶是一种合成酶.

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