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• W2042658426 abstract "Drugs that inhibit DNA topoisomerase I and DNA topoisomerase II have been widely used in cancer chemotherapy. We report herein the results of a focused medicinal chemistry effort around novel ellipticinium salts which target topoisomerase I and II enzymes with improved solubility. The salts were prepared by reaction of ellipticine with the required alkyl halide and evaluated for DNA intercalation, topoisomerase inhibition and growth inhibition against 12 cancer cell lines. Results from the topoisomerase I relaxation assay indicated that all novel ellipticine derivatives behaved as intercalating agents. At a concentration of 100 μM, specific topoisomerase I inhibition was not observed. Two of the derivatives under investigation were found to fully inhibit the DNA decatenation reaction at a concentration of 100 μM, indicative of topoisomerase II inhibition. N-Alkylation of ellipticine was found to enhance the observed growth inhibition across all cell lines and induce growth inhibition comparable to that of Irinotecan (CPT-11; GI50 1–18 μM) and in some cell lines better than Etoposide (VP-16; GI50 = 0.04–5.2 μM). 6-Methylellipticine was the most potent growth inhibitory compound assessed (GI50 = 0.47–0.9 μM). N-Alkylation of 6-methylellipticine was found to reduce this response with GI50 values in the range of 1.3–28 μM." @default.
• W2042658426 created "2016-06-24" @default.
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• W2042658426 date "2013-01-01" @default.
• W2042658426 modified "2023-10-09" @default.
• W2042658426 title "Synthesis and evaluation of novel ellipticines as potential anti-cancer agents" @default.
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• W2042658426 doi "https://doi.org/10.1039/c2ob27186a" @default.
• W2042658426 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/23314103" @default.
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