发现新型噻唑基-吡唑啉类化合物作为双重 EGFR 和 VEGFR-2 抑制剂，具有针对非小细胞肺癌的抗肿瘤活性。
Discovery of novel thiazolyl-pyrazolines as dual EGFR and VEGFR-2 inhibitors endowed with antitumor activity towards non-small lung cancer.
机构信息
Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Helwan University, Cairo, Egypt.
Department of Cellular and Molecular Medicine, University of California San Diego, La Jolla, CA, USA.
出版信息
J Enzyme Inhib Med Chem. 2022 Dec;37(1):2265-2282. doi: 10.1080/14756366.2022.2104841.
New series of thiazolyl-pyrazoline derivatives (, and ) have been synthesised and assessed for their potential EGFR and VEGFR-2 inhibitory activities. Compounds and exerted potent and selective inhibitory activity towards the two receptor tyrosine kinases; EGFR (IC = 40.7 ± 1.0 and 32.5 ± 2.2 nM, respectively) and VEGFR-2 (IC = 78.4 ± 1.5 and 43.0 ± 2.4 nM, respectively). The best anti-proliferative activity for the examined thiazolyl-pyrazolines was observed against the non-small lung cancer cells (NSCLC). Compounds and displayed pronounced efficacy against A549 (IC = 4.2 and 2.9 µM, respectively) and H441 cell lines (IC = 4.8 and 3.8 µM, respectively). Moreover, our results indicated that and were much more effective towards EGFR-mutated NSCLC cell lines (NCI-H1650 and NCI-H1975 cells) than gefitinib. Finally, compounds and induce G2/M cell cycle arrest and apoptosis and inhibit migration in A549 cancerous cells.
新系列的噻唑基-吡唑啉衍生物（、和）已经被合成，并评估了它们对 EGFR 和 VEGFR-2 的潜在抑制活性。化合物和对两种受体酪氨酸激酶具有强大而选择性的抑制活性；EGFR（IC = 40.7 ± 1.0 和 32.5 ± 2.2 nM，分别）和 VEGFR-2（IC = 78.4 ± 1.5 和 43.0 ± 2.4 nM，分别）。在所检查的噻唑基-吡唑啉中，对非小细胞肺癌细胞（NSCLC）的抗增殖活性最好。化合物和对 A549（IC = 4.2 和 2.9 μM，分别）和 H441 细胞系（IC = 4.8 和 3.8 μM，分别）表现出明显的疗效。此外，我们的结果表明，和对 EGFR 突变型 NSCLC 细胞系（NCI-H1650 和 NCI-H1975 细胞）的疗效比吉非替尼更显著。最后，化合物和诱导 A549 癌细胞的 G2/M 细胞周期停滞和凋亡，并抑制迁移。
Zotero 插件