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

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
Authors
금교창김은경이준석마무눌 하크신상철Ashraf Kareem Awad Mohammed Eldamasy박정우
Keywords
Anticancer activity; 2-Anilinoquinoline; Arylamides; Apoptosis; Cell cycle arrest; Tubulin polymerization; B-RAFV600E; C-RAF kinase
Issue Date
2020-12
Publisher
European journal of medicinal chemistry
Citation
VOL 208, 112756
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
URI
http://pubs.kist.re.kr/handle/201004/71978
ISSN
0223-5234
Appears in Collections:
KIST Publication > Article
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