Design and synthesis of novel quinoline/chalcone/1,2,4-triazole hybrids as potent antiproliferative agent targeting EGFR and BRAFV600E kinases
Design and synthesis of novel quinoline/chalcone/1,2,4-triazole hybrids as potent antiproliferative agent targeting EGFR and BRAFV600E kinases
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DOI：
10.1016/j.bioorg.2020.104510
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发表时间：
2021-01-01
影响因子：
5.1
通讯作者：
Abdel-Aziz, Mohamed
中科院分区：
文献类型：
--
作者：
Mohassab, Aliaa M.;Hassan, Heba A.;Abdel-Aziz, Mohamed
本文设计、合成了一系列新的含1，2，4-三唑结构的喹啉/查耳酮杂环化合物，并通过多种光谱技术对其结构进行了表征和确认。所设计的化合物在单剂量测定中对不同的NCI 60细胞系显示出中等至良好的活性，生长抑制率范围为50%至94%。化合物7 b、7 d、9 b和9d在大多数癌细胞系中是最具活性的化合物，生长抑制百分比在77%和94%之间。评价新合成的杂交体对一组四种人癌细胞系的抗增殖活性。化合物7a、7 b、9a、9 b和9d显示出良好的抗增殖活性。用厄洛替尼作为参比药物进一步测试这些化合物对EGFR和BRAF（V600 E）激酶的抑制效力。化合物7a、7 b、9a、9 b和9d的分子对接研究显示，它们与EGFR和BRAF（V600 E）激酶的活性位点很好地拟合。化合物7 b、9 b和9d显示出最高的结合亲和力和与厄洛替尼相似的结合模式。
New quinoline / chalcone hybrids containing 1,2,4-triazole moiety have been designed, synthesized and their structures elucidated and confirmed by various spectroscopic techniques. The designed compounds showed moderate to good activity on different NCI 60 cell lines in a single-dose assay with a growth inhibition rate ranging from 50% to 94%. Compounds 7b, 7d, 9b, and 9d were the most active compounds in most cancer cell lines with a growth inhibition percent between 77% and 94%. Newly synthesized hybrids were evaluated for their anti-proliferative activity against a panel of four human cancer cell lines. Compounds 7a, 7b, 9a, 9b, and 9d showed promising antiproliferative activities. These compounds were further tested for their inhibitory potency against EGFR and BRAF(V600E )kinases with erlotinib as a reference drug. The molecular docking study of compounds 7a, 7b, 9a, 9b, and 9d revealed nice fitting into the active site of EGFR and BRAF(V600E) kinases. Compounds 7b, 9b, and 9d displayed the highest binding affinities and similar binding pattern to those of erlotinib.