a Pharmaceutical Organic Chemistry Department, Faculty of Pharmacy , Cairo University , Cairo , Egypt.
b Pharmaceutical Chemistry Department, Faculty of Pharmacy , Nahda University , Beni Suef , Egypt.
J Enzyme Inhib Med Chem. 2019 Dec;34(1):1347-1367. doi: 10.1080/14756366.2019.1642883.
In the designed compounds, either a biarylamide or biarylurea moiety or an N-substituted piperazine motif was linked to position 1 of the phthalazine core. The anti-proliferative activity of the synthesised compounds revealed that eight compounds () exhibited excellent broad spectrum cytotoxic activity in NCI 5-log dose assays against the full 60 cell panel with GI values ranging from 0.15 to 8.41 µM. Moreover, the enzymatic assessment of the synthesised compounds against VEGFR-2 tyrosine kinase showed the significant inhibitory activities of the biarylureas () with ICs of 4.4, 2.7 and 2.5 μM, respectively, and with 79.83, 72.58 and 71.6% inhibition of HUVEC at 10 μM, respectively. Additionally, compounds ( were found to induce cell cycle arrest at S phase boundary. Compound triggered a concurrent increase in cleaved caspase-3 expression level, indicating the apoptotic-induced cell death.
在设计的化合物中，要么是联苯甲酰胺或联苯脲部分，要么是 N-取代哌嗪基序连接到苯并嗪核的 1 位。所合成化合物的抗增殖活性表明，有 8 种化合物（）在 NCI 5 对数剂量测定中对完整的 60 个细胞系表现出优异的广谱细胞毒性活性，GI 值范围为 0.15 至 8.41 μM。此外，对合成化合物对 VEGFR-2 酪氨酸激酶的酶评估表明，联苯脲（）具有显著的抑制活性，IC 分别为 4.4、2.7 和 2.5 μM，在 10 μM 时对 HUVEC 的抑制率分别为 79.83%、72.58%和 71.6%。此外，化合物（）被发现诱导细胞周期停滞在 S 期边界。化合物 触发了裂解 caspase-3 表达水平的同时增加，表明诱导细胞凋亡死亡。
