State Key Laboratory Basis of Xinjiang Indigenous Medicinal Plants Resource Utilization, Xinjiang Technical Institute of Physics and Chemistry, Chinese Academy of Sciences, South Beijing Rd 40-1, Urumqi, 830011, P. R. China.
University of Chinese Academy of Sciences, 19 A Yuquan Rd, Beijing, 100049, P. R. China.
Chem Biodivers. 2023 Mar;20(3):e202201059. doi: 10.1002/cbdv.202201059. Epub 2023 Feb 9.
The chemical transformation of the tricyclic furo[2,3-d]pyrimidines was performed under isosteric and scaffold-hopping strategies focusing on the synthesis of its arylidene and imine-containing derivatives. Naturally-occurring alkaloids mackinazolinone and isaindigotone were as templates of target heterocycles. Synthesized compounds evaluated for their antitumor activity on human cancer cervical HeLa, breast MCF-7, and colon HT-29 cell lines. Four compounds: 8c, 8e, 10b, and 10c demonstrated potency against HeLa and HT-29 cell lines, and IC values were between 7.37-13.72 μM, respectively. The molecular docking results showed that compounds 8c and 10b had good binding and high matching with the target EGFR protein.
三环[2,3-d]嘧啶的化学转化是在等排和支架跳跃策略下进行的，重点是合成其芳基烯和亚胺衍生物。天然存在的生物碱 Mackinazolinone 和 Isaindigotone 是目标杂环的模板。合成的化合物对人宫颈癌细胞系 HeLa、乳腺癌 MCF-7 和结肠癌 HT-29 进行了抗肿瘤活性评估。四种化合物：8c、8e、10b 和 10c 对 HeLa 和 HT-29 细胞系表现出活性，IC 值分别在 7.37-13.72 μM 之间。分子对接结果表明，化合物 8c 和 10b 与靶标 EGFR 蛋白具有良好的结合和高匹配性。
