2-Anilinoquinoline based arylamides as broad spectrum anticancer agents with B-RAFV600E/C-RAF kinase inhibitory effects: Design, synthesis, in vitro cell-based and oncogenic kinase assessments
DC Field | Value | Language |
---|---|---|
dc.contributor.author | El-Damasy, A.K. | - |
dc.contributor.author | Haque, M.M. | - |
dc.contributor.author | Park, J.W. | - |
dc.contributor.author | Shin, S.C. | - |
dc.contributor.author | Lee, J.-S. | - |
dc.contributor.author | EunKyeong, Kim E. | - |
dc.contributor.author | Keum, G. | - |
dc.date.accessioned | 2021-08-31T19:19:23Z | - |
dc.date.available | 2021-08-31T19:19:23Z | - |
dc.date.created | 2021-06-17 | - |
dc.date.issued | 2020 | - |
dc.identifier.issn | 0223-5234 | - |
dc.identifier.uri | https://scholar.korea.ac.kr/handle/2021.sw.korea/60726 | - |
dc.description.abstract | Prompted by the urgent demand for identification of new anticancer agents with improved potency and efficacy, a new series of arylamides incorporating the privileged 2-anilinoquinoline scaffold has been designed, synthesized, and biologically assessed. Aiming at extensive evaluation of the target compounds’ potency and spectrum, a panel of 60 clinically important cancer cell lines representing nine cancer types has been used. Compounds 9a and 9c, with piperazine substituted phenyl ring, emerged as the most active members surpassing the anticancer potencies of the FDA-approved drug imatinib. They elicited sub-micromolar or one-digit micromolar GI50 values over the majority of tested cancer cells including multidrug resistant (MDR) cells like colon HCT-15, renal TK-10 and UO-31, and ovarian NCI/ADR-RES. In vitro mechanistic study showed that compounds 9a and 9c could trigger morphological changes, apoptosis and cell cycle arrest in HCT-116 colon cancer cells. Besides, compound 9c altered microtubule polymerization pattern in a similar fashion to paclitaxel. Kinase screening of 9c disclosed its inhibitory activity over B-RAFV600E and C-RAF kinases with IC50 values of 0.888 μM and 0.229 μM, respectively. Taken together, the current report presents compounds 9a and 9c as promising broad-spectrum potent anticancer candidates, which could be considered for further development of new anticancer drugs. © 2020 | - |
dc.language | English | - |
dc.language.iso | en | - |
dc.publisher | Elsevier Masson s.r.l. | - |
dc.subject | 3 (4 ethylpiperazin 1 yl) n (3 ((5 methoxyquinolin 2 yl)amino)phenyl) 5 (trifluoromethyl)benzamide | - |
dc.subject | amide | - |
dc.subject | aniline derivative | - |
dc.subject | antineoplastic agent | - |
dc.subject | B Raf kinase | - |
dc.subject | imatinib | - |
dc.subject | n (3 ((5 methoxyquinolin 2 yl)amino)phenyl) 4 (4 methylpiperazin 1 yl) 3 (trifluoromethyl)benzamide | - |
dc.subject | paclitaxel | - |
dc.subject | phenyl group | - |
dc.subject | piperazine derivative | - |
dc.subject | polycyclic aromatic hydrocarbon derivative | - |
dc.subject | quinoline derivative | - |
dc.subject | Raf protein | - |
dc.subject | unclassified drug | - |
dc.subject | animal cell | - |
dc.subject | antineoplastic activity | - |
dc.subject | apoptosis | - |
dc.subject | Article | - |
dc.subject | cancer cell line | - |
dc.subject | cell cycle arrest | - |
dc.subject | controlled study | - |
dc.subject | drug design | - |
dc.subject | drug potency | - |
dc.subject | drug screening | - |
dc.subject | drug synthesis | - |
dc.subject | enzyme inhibition | - |
dc.subject | GI50 | - |
dc.subject | HCT 15 cell line | - |
dc.subject | human | - |
dc.subject | human cell | - |
dc.subject | IC50 | - |
dc.subject | in vitro study | - |
dc.subject | microtubule assembly | - |
dc.subject | molecular docking | - |
dc.subject | multidrug resistance | - |
dc.subject | NCI-ADR-RES cell line | - |
dc.subject | nonhuman | - |
dc.subject | oncogene | - |
dc.subject | renal cancer cell line | - |
dc.subject | structure activity relation | - |
dc.subject | UO-31 cell line | - |
dc.title | 2-Anilinoquinoline based arylamides as broad spectrum anticancer agents with B-RAFV600E/C-RAF kinase inhibitory effects: Design, synthesis, in vitro cell-based and oncogenic kinase assessments | - |
dc.type | Article | - |
dc.contributor.affiliatedAuthor | Lee, J.-S. | - |
dc.identifier.doi | 10.1016/j.ejmech.2020.112756 | - |
dc.identifier.scopusid | 2-s2.0-85090743583 | - |
dc.identifier.bibliographicCitation | European Journal of Medicinal Chemistry, v.208 | - |
dc.relation.isPartOf | European Journal of Medicinal Chemistry | - |
dc.citation.title | European Journal of Medicinal Chemistry | - |
dc.citation.volume | 208 | - |
dc.type.rims | ART | - |
dc.type.docType | Article | - |
dc.description.journalClass | 1 | - |
dc.description.journalRegisteredClass | scie | - |
dc.description.journalRegisteredClass | scopus | - |
dc.subject.keywordPlus | 3 (4 ethylpiperazin 1 yl) n (3 ((5 methoxyquinolin 2 yl)amino)phenyl) 5 (trifluoromethyl)benzamide | - |
dc.subject.keywordPlus | amide | - |
dc.subject.keywordPlus | aniline derivative | - |
dc.subject.keywordPlus | antineoplastic agent | - |
dc.subject.keywordPlus | B Raf kinase | - |
dc.subject.keywordPlus | imatinib | - |
dc.subject.keywordPlus | n (3 ((5 methoxyquinolin 2 yl)amino)phenyl) 4 (4 methylpiperazin 1 yl) 3 (trifluoromethyl)benzamide | - |
dc.subject.keywordPlus | paclitaxel | - |
dc.subject.keywordPlus | phenyl group | - |
dc.subject.keywordPlus | piperazine derivative | - |
dc.subject.keywordPlus | polycyclic aromatic hydrocarbon derivative | - |
dc.subject.keywordPlus | quinoline derivative | - |
dc.subject.keywordPlus | Raf protein | - |
dc.subject.keywordPlus | unclassified drug | - |
dc.subject.keywordPlus | animal cell | - |
dc.subject.keywordPlus | antineoplastic activity | - |
dc.subject.keywordPlus | apoptosis | - |
dc.subject.keywordPlus | Article | - |
dc.subject.keywordPlus | cancer cell line | - |
dc.subject.keywordPlus | cell cycle arrest | - |
dc.subject.keywordPlus | controlled study | - |
dc.subject.keywordPlus | drug design | - |
dc.subject.keywordPlus | drug potency | - |
dc.subject.keywordPlus | drug screening | - |
dc.subject.keywordPlus | drug synthesis | - |
dc.subject.keywordPlus | enzyme inhibition | - |
dc.subject.keywordPlus | GI50 | - |
dc.subject.keywordPlus | HCT 15 cell line | - |
dc.subject.keywordPlus | human | - |
dc.subject.keywordPlus | human cell | - |
dc.subject.keywordPlus | IC50 | - |
dc.subject.keywordPlus | in vitro study | - |
dc.subject.keywordPlus | microtubule assembly | - |
dc.subject.keywordPlus | molecular docking | - |
dc.subject.keywordPlus | multidrug resistance | - |
dc.subject.keywordPlus | NCI-ADR-RES cell line | - |
dc.subject.keywordPlus | nonhuman | - |
dc.subject.keywordPlus | oncogene | - |
dc.subject.keywordPlus | renal cancer cell line | - |
dc.subject.keywordPlus | structure activity relation | - |
dc.subject.keywordPlus | UO-31 cell line | - |
dc.subject.keywordAuthor | 2-Anilinoquinoline | - |
dc.subject.keywordAuthor | Anticancer activity | - |
dc.subject.keywordAuthor | Apoptosis | - |
dc.subject.keywordAuthor | Arylamides | - |
dc.subject.keywordAuthor | B-RAFV600E | - |
dc.subject.keywordAuthor | C-RAF kinase | - |
dc.subject.keywordAuthor | Cell cycle arrest | - |
dc.subject.keywordAuthor | Tubulin polymerization | - |
Items in ScholarWorks are protected by copyright, with all rights reserved, unless otherwise indicated.
(02841) 서울특별시 성북구 안암로 14502-3290-1114
COPYRIGHT © 2021 Korea University. All Rights Reserved.
Certain data included herein are derived from the © Web of Science of Clarivate Analytics. All rights reserved.
You may not copy or re-distribute this material in whole or in part without the prior written consent of Clarivate Analytics.