Abbas Safinaz E-S, Aly Enayat I, Awadallah Fadi M, Mahmoud Walaa R
Pharmaceutical Chemistry Department, Faculty of Pharmacy, Cairo University, Kasr El-Eini Street, 11562, Cairo, Egypt.
Chem Biol Drug Des. 2015 May;85(5):608-22. doi: 10.1111/cbdd.12451. Epub 2014 Nov 14.
Four series of some 4-substituted-1-phenyl-1H-pyrazolo[3,4-d]pyrimidine derivatives 5a-f, 6a-f, 8a-f, and 9a-f were designed to be screened for their antitumor activity. All compounds were evaluated against breast (MCF-7) and lung (A-549) cell lines. Six compounds 5a, 5b, 6b, 6e, 9e, and 9f displaying activity against both cell lines were further estimated for their EGFR-TK inhibitory activity where they revealed 41-91% inhibition and compound 6b elicited the highest activity (91%). A docking study of these compounds into the ATP-binding site of EGFR-TK demonstrated their binding mode where H-bonding interaction with Met793 through N(1) of pyrimidine or N(2) of pyrazole was observed.
设计了四类约4-取代-1-苯基-1H-吡唑并[3,4-d]嘧啶衍生物5a-f、6a-f、8a-f和9a-f，以筛选它们的抗肿瘤活性。所有化合物均针对乳腺癌（MCF-7）和肺癌（A-549）细胞系进行了评估。对六种对两种细胞系均有活性的化合物5a、5b、6b、6e、9e和9f进一步评估其EGFR-TK抑制活性，结果显示它们的抑制率为41%-91%，化合物6b活性最高（91%）。对这些化合物与EGFR-TK的ATP结合位点进行对接研究，证明了它们的结合模式，观察到嘧啶的N(1)或吡唑的N(2)与Met793之间存在氢键相互作用。
