https://scholars.lib.ntu.edu.tw/handle/123456789/597254
DC 欄位 | 值 | 語言 |
---|---|---|
dc.contributor.author | Lee, Jiann-Fong | en_US |
dc.contributor.author | Chang, Ting-Yu | en_US |
dc.contributor.author | Liu, Zheng-Fang | en_US |
dc.contributor.author | Lee, Nian-Zhe | en_US |
dc.contributor.author | Yeh, Yen-Hsiu | en_US |
dc.contributor.author | Chen, Yi-Song | en_US |
dc.contributor.author | Chen, Tsung-Chih | en_US |
dc.contributor.author | Chou, Hao-Syun | en_US |
dc.contributor.author | TSAI-KUN LI | en_US |
dc.contributor.author | Lee, Sung-Bau | en_US |
dc.contributor.author | Lin, Mei-Hsiang | en_US |
dc.date.accessioned | 2022-03-14T12:48:15Z | - |
dc.date.available | 2022-03-14T12:48:15Z | - |
dc.date.issued | 2020 | - |
dc.identifier.issn | 0223-5234 | - |
dc.identifier.uri | https://www.scopus.com/record/display.uri?eid=2-s2.0-85078999981&origin=resultslist | - |
dc.identifier.uri | https://scholars.lib.ntu.edu.tw/handle/123456789/597254 | - |
dc.description.abstract | A series of thiochromeno[2,3-c]quinolin-12-one derivatives with various substitutions were synthesized and evaluated as topoisomerase (Topo) inhibitors. Six (8, 10, 12, 14, 19, and 26) of 23 compounds showed strong inhibitory activities against Topo-mediated DNA relaxation and proliferation of five human cell lines including breast (MDA-MB-231, MDA-MB-468 and MCF7), colorectal (HCT116) and non-small cell lung (H1299) cancers. Among these, compounds 14 and 26 exhibited full inhibitory activities against Topo I at 3 μM and Topo IIα at 1 μM. Cancer cells treated with 26 accumulated DNA damage and were arrested at the G2/M phase. With time, cells proceeded to apoptosis, as revealed by increased amounts of cells with fragmented DNA and cleavage of caspase-8 and -9. In contrast, normal breast epithelial cells showed low sensitivity to 26. Taken together, our study identifies 26 as a potent Topo dual-inhibitor with low toxicity to normal cells, and elucidates that the terminal amino group of N-2-aminoethylamino or N-3-aminopropylamino at the 6th position and 8,10-di-halogen substituents on thiochromeno[2,3-c]quinolin-12-one are critical for the Topo-inhibiting and cancer-killing activities. ? 2020 Elsevier Masson SAS | - |
dc.publisher | Elsevier Masson s.r.l. | - |
dc.relation.ispartof | European Journal of Medicinal Chemistry | - |
dc.subject | Dual inhibitor; Thiochromeno[2,3-c]quinolin-12-one; Topoisomerase; VADBTZWEQZHZRE-UHFFFAOYSA-N | - |
dc.subject.classification | [SDGs]SDG3 | - |
dc.subject.other | 10 chloro 6 (propylamino) 12h thiochromeno[2,3 c]quinolin 12 one; 10 chloro 6 [(4 methoxybenzyl)amino] 12h thiochromeno [2,3 c]quinolin 12 one; 10 fluoro 6 (propylamino) 12h thiochromeno[2,3 c]quinolin 12 one; 2 hydroxy 3 (4 tolylthio)quinoline 4 carboxylic acid; 2 hydroxy 3 [(2 methoxyphenyl)thio]quinoline 4 carboxylic acid; 2 hydroxy 3 [(4 methoxyphenyl)thio]quinoline 4 carboxylic acid; 3 [(2 chloro 4 fluorophenyl)thio] 2 hydroxyquinoline 4 carboxylic acid; 3 [(2 chlorophenyl)thio] 2 hydroxyquinoline 4 carboxylic acid; 3 [(2 fluorophenyl)thio] 2 hydroxyquinoline 4 carboxylic acid; 3 [(3 chlorophenyl)thio] 2 hydroxyquinoline 4 carboxylic acid; 3 [(4 chlorophenyl)thio] 2 hydroxyquinoline 4 carboxylic acid; 3 [(4 fluorophenyl)thio] 2 hydroxyquinoline 4 carboxylic acid; 6 chloro 10 fluoro 12h thiochromeno[2,3 c]quinolin 12 one; 6 chloro 10 methoxy 12h thiochromeno[2,3 c]quinolin 12 one; 6 chloro 10 methyl 12h thiochromeno[2,3 c]quinolin 12 one; 6 chloro 8 fluoro 12h thiochromeno[2,3 c]quinolin 12 one; 6 chloro 8 methoxy 12h thiochromeno[2,3 c]quinolin 12 one; 6 [(3 aminopropyl)amino] 10 chloro 12h thiochromeno [2,3 c]quinolin 12 one; 6,10 dichloro-12h thiochromeno[2,3 c]quinolin 12 one; 6,8 dichloro 10 fluoro 12h thiochromeno[2,3 c]quinolin 12 one; 6,8 dichloro 12h thiochromeno[2,3 c]quinolin 12 one; 6,9 dichloro 12h thiochromeno[2,3 c]quinolin 12 one; antineoplastic agent; camptothecin; caspase 9; DNA topoisomerase; n (10 chloro 12 oxo 12h thiochromeno[2,3 c]quinolin 6 yl) picolinamide; quinoline derivative; quinolinone derivative; unclassified drug; unindexed drug; antiproliferative activity; apoptosis; aqueous solution; Article; cell viability; controlled study; DNA damage; DNA fragmentation; drug design; drug screening; drug synthesis; HCT 116 cell line; human; human cell; MCF-7 cell line; MDA-MB-231 cell line; MDA-MB-468 cell line; NCI-H1299 cell line; protein cleavage; proton nuclear magnetic resonance; structure activity relation; retraction notice | - |
dc.title | Design, synthesis, and biological evaluation of heterotetracyclic quinolinone derivatives as anticancer agents targeting topoisomerases | en_US |
dc.type | retracted | en |
dc.identifier.doi | 10.1016/j.ejmech.2020.112074 | - |
dc.identifier.pmid | 32045788 | - |
dc.identifier.scopus | 2-s2.0-85078999981 | - |
dc.relation.journalvolume | 190 | - |
item.fulltext | no fulltext | - |
item.cerifentitytype | Publications | - |
item.openairetype | retracted | - |
item.openairecristype | http://purl.org/coar/resource_type/c_18cf | - |
item.grantfulltext | none | - |
crisitem.author.dept | Microbiology | - |
crisitem.author.dept | Center for Biotechnology | - |
crisitem.author.orcid | 0000-0003-0393-2340 | - |
crisitem.author.parentorg | College of Medicine | - |
crisitem.author.parentorg | Others: University-Level Research Centers | - |
顯示於: | 微生物學科所 |
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