El-Damasy, Ashraf Kareem Seo, Seon Hee Cho, Nam-Chul Kang, Soon Bang Pae, Ae Nim Kim, Key-Sun Keum, Gyochang 2024-01-20T06:32:04Z 2024-01-20T06:32:04Z 2021-09-05 2015-08 0223-5234 https://pubs.kist.re.kr/handle/201004/125162 New 2-amido and ureido quinoline derivatives substituted with 2-N-methylamido-pyridin-4-yloxy group at the 5-position of quinoline (18 final compounds) have been designed and synthesized as anticancer sorafenib congeners. Among the synthesized derivatives, fourteen compounds were selected for evaluation of their antiproliferative activity over a panel of 60 cancer cell lines at a single dose concentration of 10 mu M at National Cancer Institute (NCI, USA). Four compounds, 9b-d and 9f showed promising mean growth inhibitions and thus were further tested at five-dose testing mode to determine their IC50 values. The data revealed that 2,4-difluorophenyl (9b) and 4-chloro-3-trifluoromethylphenyl (9d) urea compounds are the most active derivatives with significant efficacies and superior potencies than sorafenib in 36 and 12 cancer cell lines, respectively, belonging particularly to renal carcinoma cell (RCC), ovarian, and non small cell lung cancer (NSCL). Compound 9b and 9d were found to be six and two times more potent than sorafenib against A498 RCC line, with IC50 values of 0.42 mu M and 1.36 mu M, respectively. Accordingly, compound 9d was screened over a panel of 41 oncogenic kinases at a single dose concentration of 10 mu M to profile its kinase inhibitory activity. Interestingly, the compound showed highly selective inhibitory activities (81.8% and 96.3%) against BRAF(V600E) and C-RAF kinases with IC50 values of 316 nM and 61 nM, respectively. In addition, molecular docking, cell cycle analysis, compliance to Lipinski's rule of five, and in silico toxicity assessment have been reported. (C) 2015 Elsevier Masson SAS. All rights reserved. English ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER Design, synthesis, in-vitro antiproliferative activity and kinase profile of new picolinamide based 2-amido and ureido quinoline derivatives Article 10.1016/j.ejmech.2015.07.025 1 EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, v.101, pp.754 - 768 EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY 101 754 768 N scie scopus 000360771900064 2-s2.0-84938065195 Chemistry, Medicinal Pharmacology & Pharmacy Article ADVANCED HEPATOCELLULAR-CARCINOMA RENAL-CELL CARCINOMA B-RAF MULTIKINASE INHIBITOR CANCER-TREATMENT OVARIAN-CANCER LUNG-CANCER SORAFENIB MELANOMA GROWTH Antiproliferative activity Quinoline Urea Amide Picolinamide BRAF(V600E) C-RAF