Pharmaceutical Chemistry Department, Faculty of Pharmacy, Cairo University, Cairo 11562, Egypt.
Organic Chemistry Department, National Organization For Drug & Control Research, Cairo, Egypt.
Bioorg Chem. 2019 Mar;83:186-197. doi: 10.1016/j.bioorg.2018.10.038. Epub 2018 Oct 20.
Quinoline derivatives 2, 3, quinolinyl based pyrazolines 4a,b, 5 and quinolinyl pyrazolinyl thiazole hybrids 6a-d, 7a-c and 8a-d were synthesized and screened for their anti-proliferative activity against MCF-7, HeLa and DLD1 cancer cell lines as well as normal fibroblast WI-38. Most of the tested compounds showed promising anticancer activity in addition to their safety towards the normal cell line. Eight compounds eliciting superior cytotoxicity against DLD1 and safe to the normal cell line 2, 3, 5, 6a, 6b, 7b, 7c and 8a were evaluated for their efficacy as EGFR inhibitors. They revealed inhibitory activity at nanomolar level especially compounds 6b, 2 and 7c with IC (31.80, 37.07 and 42.52 nM) in comparison to Gefitinib (IC = 29.16 nM).
喹啉衍生物 2、3、基于喹啉的吡唑啉 4a、b、5 和喹啉吡唑啉噻唑杂合体 6a-d、7a-c 和 8a-d 被合成并筛选其对 MCF-7、HeLa 和 DLD1 癌细胞系以及正常成纤维细胞 WI-38 的抗增殖活性。大多数测试的化合物除了对正常细胞系安全外，还表现出有希望的抗癌活性。对 DLD1 具有优异细胞毒性且对正常细胞系安全的 8 种化合物 2、3、5、6a、6b、7b、7c 和 8a 被评估为 EGFR 抑制剂的功效。它们在纳摩尔水平显示出抑制活性，特别是化合物 6b、2 和 7c，其 IC（31.80、37.07 和 42.52 nM）与 Gefitinib（IC=29.16 nM）相比。
