Medicinal &Pharmaceutical Chemistry Department, Pharmaceutical and Drug Industries Research Division, National Research Centre (NRC ID: 60014618), Dokki, Giza 12622, Egypt.
Center for Biomaterials, Korea Institute of Science & Technology (KIST School), Seoul, Seongbuk-gu 02792, Republic of Korea; University of Science & Technology (UST), Daejeon, Yuseong-gu 34113, Republic of Korea; Pharmaceutical Chemistry Department, Faculty of Pharmacy, Modern University of Technology and Information (MTI), Cairo 12055, Egypt.
Bioorg Med Chem. 2020 Jun 1;28(11):115493. doi: 10.1016/j.bmc.2020.115493. Epub 2020 Apr 10.
Several pyrrolo[2,3-b]pyridine-based B-RAF inhibitors are well known and some of them are currently FDA approved as anticancer agents. Based on the structure of these FDA approved B-RAF inhibitors, two series of pyrrolo[2,3-b]pyridine scaffold were designed and synthesized in attempt to develop new potent B-RAF inhibitors. The 38 synthesized compounds were biologically evaluated for their B-RAF inhibitory effect at single dose (10 μM). Compounds with high percent inhibition were tested to determine their IC over B-RAF. Compounds 34e and 35 showed the highest inhibitory effect with IC values of 0.085 µM and 0.080 µM, respectively. Headed for excessive biological evaluation, the synthesized derivatives were tested over sixty diverse human cancer cell lines. Only compound 35 emerged as a potent cytotoxic agent against different panel of human cancer cell lines.
几种吡咯并[2,3-b]吡啶基 B-RAF 抑制剂广为人知，其中一些已被 FDA 批准为抗癌药物。基于这些已获 FDA 批准的 B-RAF 抑制剂的结构，我们设计并合成了两个系列的吡咯并[2,3-b]吡啶骨架，试图开发新的强效 B-RAF 抑制剂。我们对 38 种合成化合物进行了单剂量（10 μM）的 B-RAF 抑制活性的生物学评估。对高抑制百分比的化合物进行了 IC 50 over B-RAF 的测试。化合物 34e 和 35 的抑制效果最强，IC 值分别为 0.085 µM 和 0.080 µM。为了进行过度的生物学评价，我们对六十多种不同的人癌细胞系进行了合成衍生物的测试。只有化合物 35 对不同的人癌细胞系panel 表现出了强效的细胞毒性。
