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The cytotoxicity of these compounds was determined using three breast tumor cell lines (MDA-MB231, MDA-MB468 and MCF7) and two matching non-cancer breast epithelial cell lines (184B5 and MCF10A). Although most of the compounds were quite effective on the breast cancer cells, the compound 7-chloro-4-(4-(2,4-dinitrophenylsulfonyl)piperazin-1-yl)quinoline (<jats:bold>13<\/jats:bold>; VR23) emerged as potentially the most desirable one in this series of compounds. Data from the NCI-60 cancer panel screening show that compound <jats:bold>13<\/jats:bold> is effective on a wide range of different cancers. Importantly, compound <jats:bold>13<\/jats:bold> is needed up to 17.6-fold less doses to achieve the same IC<jats:sub>50<\/jats:sub> against cancer than non-cancer cells (MDA-MB468 <jats:italic>vs<\/jats:italic> MCF10A), suggesting that it can potentially be less toxic to normal cells. Cancer cells formed multiple centrosomes in the presence of compound <jats:bold>13<\/jats:bold>, resulting in the cell cycle arrest at prometa-meta phase. This abnormality leads to eventual cell demise with sub-G1 DNA content typically shown with apoptotic cells. In addition, compound <jats:bold>13<\/jats:bold> also causes an increase in lysosomal volume in cancer but not in non-cancer cells, which may contribute at least in part to its preferential cancer cell-killing. The cancer cell-killing effect of compound <jats:bold>13<\/jats:bold> is highly potentiated when combined with either bortezomib or monastrol.<\/jats:p>","DOI":"10.1038\/s41598-019-42816-4","type":"journal-article","created":{"date-parts":[[2019,4,19]],"date-time":"2019-04-19T10:02:29Z","timestamp":1555668149000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":38,"title":["Examination of novel 4-aminoquinoline derivatives designed and synthesized by a hybrid pharmacophore approach to enhance their anticancer activities"],"prefix":"10.1038","volume":"9","author":[{"given":"V. 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