Anticancer, antimicrobial activities of quinoline based hydrazone analogues: Synthesis, characterization and molecular docking
Anticancer, antimicrobial activities of quinoline based hydrazone analogues: Synthesis, characterization and molecular docking
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DOI：
10.1016/j.bioorg.2019.103406
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发表时间：
2020-01-01
影响因子：
5.1
通讯作者：
Reddy, Dushyanth
中科院分区：
文献类型：
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作者：
Katariya, Kanubhai D.;Shah, Shailesh R.;Reddy, Dushyanth
以具有生物活性的杂环喹啉为基础，以6-溴/6-氯-2-甲基-喹啉-4-基肼为原料，制备了一系列(18a-p)喹啉腙类似物。所有新合成的化合物的细胞毒性活性均在美国国家癌症研究所 (NCI) 进行，针对完整的 NCI 60 人类癌细胞系。在所有测试的化合物中，九种化合物（18b、18d、18e、18f、18g、18h、18i、18j、18l）在10μM浓度下表现出重要的抗增殖活性，并在五种不同浓度（0.01、0.1、1、10和100μM）的10倍稀释度下进一步筛选GI（50）值范围为0.33至4.87μM，LC50值范围为4.67μM至> 100jμM。此外，将最有效的化合物18j的GI（50）、TGI和LC50平均值与临床使用的抗癌药物苯达莫司汀和苯丁酸氮芥进行比较，表明喹啉腙有望成为潜在的抗癌药物代理。此外，还对所有新制备的化合物的抗菌活性进行了筛选。所有喹啉腙对测试的致病菌株均表现出良好至优异的抗菌活性，MIC 值范围为 6.25 至 100 μg/mL。将合成的化合物与人 DNA 拓扑异构酶 I (htopoI) 的活性结合位点进行分子对接，以预测与 DNA 拓扑异构酶 I 抑制剂的结合模式。希望在未来，基于喹啉核心的化合物可以用作设计新抗癌药物的先导化合物。
Based on the biologically active heterocycle quinoline, a series (18a-p) of quinoline hydrazone analogues were prepared, starting from 6-bromo/6-chloro-2-methyl-quinolin-4-yl-hydrazines. For all the newly synthesized compounds cytotoxic activities were carried out at the National Cancer Institute (NCI), USA, against full NCI 60 human cancer cell lines. Amongst all the tested compounds, nine compounds (18b, 18d, 18e, 18f, 18g, 18h, 18i, 18j, 18l) exhibited important anti-proliferative activity at 10 mu M concentration and were further screened at 10-fold dilutions of five different concentrations (0.01, 0.1, 1, 10 and 100 mu M) with GI(50) values ranging from 0.33 to 4.87 mu M and LC50 values ranging from 4.67 mu M to > 100j mu M. Further, the mean values of GI(50), TGI and LC50 of the most potent compound 18j were compared with the clinically used anticancer agents bendamustine and chlorambucil, revealed that the quinolyl hydrazones holds promise as a potential anticancer agents. Further all the newly prepared compounds were screened for their antimicrobial activity. All the quinolyl hydrazones displayed good to excellent antimicrobial activity with MIC values ranging from 6.25 to 100 mu g/mL against the tested pathogenic strains. Molecular docking of the synthesized compounds into the active binding site of human DNA topoisomerase I (htopoI) was carried out to predict the binding mode to the DNA topoisomerase I inhibitors. Hopefully in future, compounds based on quinoline core could be used as a lead compounds for designing new anticancer agents.