Pharmaceutical Chemistry Department, Faculty of Pharmacy, Cairo University, Cairo 11562, Egypt.
University of Science and Technology, Zewail City of Science and Technology, Cairo, 12588, Egypt.
Mini Rev Med Chem. 2018;18(20):1759-1774. doi: 10.2174/1389557518666180903153254.
BACKGROUND & METHOD: A series of thirty-one new 1-phthalazinones was designed and synthesized based on the well-known VEGFR inhibitor vatalanib. The obtained phthalazinones were screened for their cytotoxic activity against DLD-1 and LoVo (colon), and Panc-1 and Paca-2 (pancreas) cancer cell lines using MTT assay. The tested compounds revealed exceptionally promising cytotoxic activity against LoVo cell lines with IC50 ranges 0.18-780 nM.
Finally, these compounds were also found to be dual inhibitors of VEGFR-2 and EGFR in the in vitro enzyme assay with higher potency against the former (IC50 = 0.023-0.41 nM).
基于著名的 VEGFR 抑制剂凡德他尼，设计并合成了一系列 31 种新的 1-酞嗪酮。采用 MTT 法，对所得到的酞嗪酮进行了对 DLD-1 和 LoVo（结肠）、Panc-1 和 Paca-2（胰腺）癌细胞系的细胞毒性筛选。测试化合物对 LoVo 细胞系具有异常有前途的细胞毒性，IC50 范围为 0.18-780 nM。
最后，这些化合物也被发现是 VEGFR-2 和 EGFR 的体外酶抑制剂双重抑制剂，对前者的抑制作用更强（IC50=0.023-0.41 nM）。
