发现新型噻吩并[2,3-d]嘧啶类作为治疗癌症的表皮生长因子受体酪氨酸激酶抑制剂。
Discovery of new thieno[2,3-]pyrimidines as EGFR tyrosine kinase inhibitors for cancer treatment.
机构信息
Pharmaceutical Chemistry Department, Faculty of Pharmacy, Menoufia University, Menoufia, Egypt.
Pharmaceutical Medicinal Chemistry & Drug Design Department, Faculty of Pharmacy (Boys), Al-Azhar University, Cairo, 11884, Egypt.
出版信息
Future Med Chem. 2023 Jul;15(13):1167-1184. doi: 10.4155/fmc-2023-0086. Epub 2023 Aug 2.
EGFR has been considered a vital molecular target in cancer management. The discovery of new thieno[2,3-]pyrimidine derivatives as EGFR tyrosine kinase inhibitors. Nine derivatives were designed, synthesized and subjected to and studies. Compound significantly inhibited the growth of HepG2 and PC3 cells for both EGFR wild-type and EGFR. Compound caused a significant apoptotic effect, arresting HepG2 cells' growth in the S and G2/M phases. Docking and molecular dynamics simulation studies confirmed the correct and stable binding modes of the synthesized compounds against the active sites. Compound is a promising dual EGFR inhibitor for cancer treatment.
表皮生长因子受体 (EGFR) 已被认为是癌症管理中至关重要的分子靶标。本研究发现新型噻吩并[2,3-d]嘧啶衍生物作为 EGFR 酪氨酸激酶抑制剂。设计、合成并进行了 9 个衍生物的 EGFR 抑制活性和抗肿瘤活性筛选。化合物 显著抑制 EGFR 野生型和 EGFR 突变型 HepG2 和 PC3 细胞的生长。化合物 引起明显的凋亡作用，将 HepG2 细胞的生长阻滞在 S 和 G2/M 期。对接和分子动力学模拟研究证实了合成化合物与活性部位的正确和稳定的结合模式。化合物 是一种有前途的双重 EGFR 抑制剂，可用于癌症治疗。
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