喹唑啉酮-氨基酸杂合体作为 EGFR 激酶和微管蛋白聚合的双重抑制剂。
Quinazolinone-Amino Acid Hybrids as Dual Inhibitors of EGFR Kinase and Tubulin Polymerization.
机构信息
Department of Pharmacognosy and Pharmaceutical Chemistry, College of Pharmacy, Taibah University, Al-Madinah 41477, Al-Munawarah, Saudi Arabia.
Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Al-Azhar University, Cairo 11884, Egypt.
出版信息
Molecules. 2018 Jul 12;23(7):1699. doi: 10.3390/molecules23071699.
Some fluoroquinazolinones (⁻) were designed, synthesized and biologically evaluated for their antitumor activity against the two cell lines, MCF-7 and MDA-MBA-231. New derivative (IC = 0.44 ± 0.01 µM) showed antitumor activity, better than that of the reference drug erlotinib (IC = 1.14 ± 0.04 µM) against MCF-7. New derivative (IC = 0.43 ± 0.02 µM) showed higher activity than the reference drug erlotinib (IC = 2.55 ± 0.19 µM) against MDA-MBA-231. Furthermore, the EGFR (epidermal growth factor receptor) and tubulin inhibition assays were carried out for the highest active derivatives to reveal the expected mechanism of action. They exhibited significant results compared to the reference drugs. Molecular docking simulations were performed on EGFR and tubulin binding sites to rationalize the experimental results and describe their binding modes. The results of the molecular modeling study were correlated with that of the antitumor screening.
一些氟喹诺酮类化合物（⁻）被设计、合成并进行了抗肿瘤活性评价，针对 MCF-7 和 MDA-MBA-231 两种细胞系。新衍生物 （IC = 0.44 ± 0.01 µM）显示出抗肿瘤活性，优于参考药物厄洛替尼（IC = 1.14 ± 0.04 µM）对 MCF-7 的活性。新衍生物 （IC = 0.43 ± 0.02 µM）对 MDA-MBA-231 的活性高于参考药物厄洛替尼（IC = 2.55 ± 0.19 µM）。此外，还对最高活性衍生物进行了 EGFR（表皮生长因子受体）和微管蛋白抑制试验，以揭示预期的作用机制。与参比药物相比，它们显示出显著的效果。对 EGFR 和微管蛋白结合部位进行了分子对接模拟，以合理化实验结果并描述其结合模式。分子建模研究的结果与抗肿瘤筛选结果相关。
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