Full metadata record
DC Field | Value | Language |
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dc.contributor.author | 권영주 | * |
dc.contributor.author | 전규연 | * |
dc.date.accessioned | 2016-08-27T04:08:01Z | - |
dc.date.available | 2016-08-27T04:08:01Z | - |
dc.date.issued | 2016 | * |
dc.identifier.issn | 0968-0896 | * |
dc.identifier.issn | 1464-3391 | * |
dc.identifier.other | OAK-16637 | * |
dc.identifier.uri | https://dspace.ewha.ac.kr/handle/2015.oak/218111 | - |
dc.description.abstract | A series of pyrazoline derivatives (5) were synthesized in 92-96% yields from chalcones (3) and hydrazides (4). Subsequently, topo-I and II alpha-mediated relaxation and antiproliferative activity assays were evaluated for 5. Among the tested compounds, 5h had a very strong topo-I activity of 97% (Camptothecin, 74%) at concentration of 100 mu M. Nevertheless, all the compounds 5a-5i showed significant topo II inhibitory activity in the range of 90-94% (Etoposide, 96%) at the same concentration. Cytotoxic potential of these compounds was tested in a panel of three human tumor cell lines, HCT15, BT474 and T47D. All the compounds showed strong activity against HCT15 cell line with IC50 at the range of 1.9-10.4 mu M (Adriamycin, 23.0; Etoposide, 6.9; and Camptothecin, 7.1 mu M). Moreover, compounds 5c, 5f and 5i were observed to have strong antiproliferative activity against BT474 cell lines. Since, compound 5d showed antiproliferative activity at a very low IC50 thus 5d was then selected to study on their mode of action with diverse methods of ATP competition assay, ATPase assay and DNA-topo II alpha cleavable complex assay and the results revealed that it functioned as a ATP-competitive human topoisomerase II alpha catalytic inhibitor. Further evaluation of endogenous topo-mediated DNA relaxation in cells has been conducted to find that, 5d inhibited endogenous topo-mediated pBR322 plasmid relaxation is more efficient (78.0 +/- 4.7% at 50 mu M) than Etoposide (36.0 +/- 1.7% at 50 mu M). (C) 2016 Elsevier Ltd. All rights reserved. | * |
dc.language | English | * |
dc.publisher | PERGAMON-ELSEVIER SCIENCE LTD | * |
dc.subject | Pyrazoline derivatives | * |
dc.subject | Antiproliferative activity | * |
dc.subject | Topoisomerase | * |
dc.subject | ATP-competitive inhibitor | * |
dc.title | Design, synthesis, topoisomerase I & II inhibitory activity, antiproliferative activity, and structure-activity relationship study of pyrazoline derivatives: An ATP-competitive human topoisomerase II alpha catalytic inhibitor | * |
dc.type | Article | * |
dc.relation.issue | 8 | * |
dc.relation.volume | 24 | * |
dc.relation.index | SCI | * |
dc.relation.index | SCIE | * |
dc.relation.index | SCOPUS | * |
dc.relation.startpage | 1898 | * |
dc.relation.lastpage | 1908 | * |
dc.relation.journaltitle | BIOORGANIC & MEDICINAL CHEMISTRY | * |
dc.identifier.doi | 10.1016/j.bmc.2016.03.017 | * |
dc.identifier.wosid | WOS:000372592900031 | * |
dc.identifier.scopusid | 2-s2.0-84960540756 | * |
dc.author.google | Ahmad, Pervez | * |
dc.author.google | Woo, Hyunjung | * |
dc.author.google | Jun, Kyu-Yeon | * |
dc.author.google | Kadi, Adnan A. | * |
dc.author.google | Abdel-Aziz, Hatem A. | * |
dc.author.google | Kwon, Youngjoo | * |
dc.author.google | Rahman, A. F. M. Motiur | * |
dc.contributor.scopusid | 권영주(12446435600) | * |
dc.contributor.scopusid | 전규연(25632526500) | * |
dc.date.modifydate | 20240422124907 | * |