新型二皮里米丁作为有前途的EGFR和HER2抑制剂:实验和计算研究的见解
Syed Faizan1, Adil Farooq Wali2, Sirajunisa Talath2
1Department of Pharmaceutical Chemistry, JSS College of Pharmacy, Mysuru 570015, Constituent College of the JSS Academy of Higher Education & Research, Mysuru, 570015, India.
European journal of medicinal chemistry
|June 22, 2024
概括
新型Biginelli二胺显示出显著的抗癌活性. 化合物16,21和39有效抑制EGFR和HER2,为癌症治疗提供双重抑制剂的潜力.
科学领域:
- 药用化学 医学化学
- 有机合成 有机合成
- 药理学 药理学是指药理学的学科.
背景情况:
- 通过比尼内利反应合成的二皮里米丁具有多种生物活性.
- 向像EGFR和HER2这样的受体氨酸激酶在癌症治疗中至关重要.
研究的目的:
- 设计,合成和评估新型Biginelli二胺的抗癌性质.
- 研究它们作为EGFR和HER2的双重抑制剂的潜力.
主要方法:
- 合成和表征38种新的Biginelli二胺基.
- 在体外细胞毒性测定对MCF-7乳腺癌和Vero细胞.
- 流细胞计,EGFR/HER2表达抑制试验和EGFRwt激酶抑制试验.
- 3D-QSAR和分子对接用于结构-活性关系和验证.
主要成果:
- 化合物16,21和39对MCF-7细胞表现出显著的细胞毒性.
- 化合物21在1000nm时实现了98.51%的EGFR和96.79%的HER2抑制.
- 化合物16,21和39表现出强大的EGFRwt抑制,IC50值在37.21至76.79nM之间.
结论:
- 成功开发出了一系列新的Biginelli二胺酸.
- 化合物16,21和39被确定为有前途的EGFR/HER2双抑制剂.
- 这些化合物有可能在癌症治疗中进一步发展.
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