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鉴定新型CA IX抑制剂:药模拟,对接,DFT和动态模拟

Shakthi Devi Packiapalavesam¹, Venkatesan Saravanan¹, Anand A Mahajan²

¹Department of Pharmaceutical Chemistry, SRM College of Pharmacy, SRM Institute of Science and Technology, Chengalpattu District, Kattankulathur, Tamil Nadu 603203, India.

Computational biology and chemistry

|April 28, 2024

概括

研究人员确定了人类碳酸无水酶IX (hCA IX) 的有前途的新抑制剂,这是缺氧瘤中的关键生物标志物. 化合物S35由于其稳定性和电子性质,具有选择性癌症治疗的特殊潜力.

科学领域:

生物化学生化学
计算化学的计算化学
在瘤学瘤学.

背景情况:

人类碳酸无水酶IX (hCA IX) 是缺氧瘤的关键生物标志物.
hCA IX在维持pH值方面起着至关重要的作用,在低氧条件下表达过度,使其成为癌症治疗的目标.

研究的目的:

开发一种用于识别选择性hCA IX抑制剂的药模型.
发现针对癌症治疗的hCA IX的新型化合物.

主要方法:

使用天然产品抑制剂 (IC50 < 50 nM) 开发了一种药模型.
采用分子对接和分子动力学 (MD) 模拟来分析蛋白质 - 连接体相互作用.
用密度函数理论 (DFT) 进行量子研究 (HOMO-LUMO差距).

主要成果:

从数据库中确定了186个潜在的结果,与关键残留物有良好的相互作用 (HIS94,HIS96,HIS119,THR199,ZN301).
MD模拟 (100 ns) 评估了顶部化合物的稳定性,随后进行了具有约束力的自由能量计算.
DFT的研究证实了能量变化,并强调了S35化合物的稳定性和更小的能量差距.

结论:

发现有前途的化合物,具有作为选择性hCA IX抑制剂的潜力.
三种化合物显示出显著的潜力,其中化合物S35被确定为选择性CA IX抑制的理想候选者.

关键词:

碳酸无水酶是一种碳酸无水酶.低毒性瘤的发生分子模拟分子模拟制药学模型的建模.量子力学计算中的量子力学计算

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