El-Damasy, Ashraf K. Haque, Md Mamunul Park, Jung Woo Shin, Sang Chul Lee, Jun-Seok Kim, Eunice EunKyeong Keum, Gyochang 2024-01-19T16:00:54Z 2024-01-19T16:00:54Z 2021-09-02 2020-12 0223-5234 https://pubs.kist.re.kr/handle/201004/117677 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 GI(50) 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 mu M and 0.229 mu M, 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. (c) 2020 Published by Elsevier Masson SAS. English Elsevier BV 2-Anilinoquinoline based arylamides as broad spectrum anticancer agents with B-RAF(V600E)/C-RAF kinase inhibitory effects: Design, synthesis, in vitro cell-based and oncogenic kinase assessments Article 10.1016/j.ejmech.2020.112756 1 European Journal of Medicinal Chemistry, v.208 European Journal of Medicinal Chemistry 208 N scie scopus 000600384300015 2-s2.0-85090743583 Chemistry, Medicinal Pharmacology & Pharmacy Article BIOLOGICAL EVALUATION IMATINIB MESYLATE DRUG DISCOVERY OVARIAN-CANCER PHASE-II POTENT DERIVATIVES EFFICACY MOIETY ANTIPROLIFERATIVE ACTIVITY 2-Anilinoquinoline Arylamides Apoptosis Cell cycle arrest Tubulin polymerization B-RAF(V600E) C-RAF kinase Anticancer activity