El-Damasy, Ashraf Kareem Seo, Seon Hee Cho, Nam-Chul Pae, Ae Nim Kim, Eunice Eunkyeong Keum, Gyochang 2024-01-20T02:32:56Z 2024-01-20T02:32:56Z 2021-09-04 2017-01 1747-0277 https://pubs.kist.re.kr/handle/201004/123279 A series of new 2-anilinoquinolines 6a-o possessing the substantial N-methylpicolinamide motif at C5 has been designed and synthesized as sorafenib analogs. The antiproliferative activities of the target compounds were preliminarily appraised against a panel of three human cancer cell lines (MCF-7, SK-BR3, and HCT116), and a selected array was further tested over a panel of approximately 60 cancer cell lines at NCI at 10M concentration. Interestingly, compounds 6c, 6d, 6j, 6k, and 6l showed promising selective anticancer activities (growth inhibition >80%) toward certain cancer cells at 10M testing dose. Compounds 6d and 6j were advanced to five-dose testing mode to determine their GI(50) values and compared with our previously reported ureidoquinoline B and sorafenib as reference compounds. The 4-chloro-3-trifluoromethylaniline derivative 6j manifested superior potency than both compound B and sorafenib over eleven and eight cell lines, respectively. It showed GI(50) values of 0.36, 0.66, 0.68, and 0.60M against the breast MDA-MB-468, renal A498, and melanoma SK-MEL-5 and UACC-62 cell lines, respectively. Moreover, both 6d and 6j exerted low cytotoxic effects against HFF-1 normal cell line. Furthermore, compounds 6d and 6j were tested against both B-Raf(V600E) and C-Raf kinases and displayed modest inhibitory activities, which were justified by molecular docking study. Compound 6j could serve as a promising candidate for further development of potent anticancer chemotherapeutics. English WILEY RAF KINASE INHIBITORS ADVANCED HEPATOCELLULAR-CARCINOMA MULTIKINASE INHIBITOR BRAF INHIBITORS B-RAF SORAFENIB DISCOVERY MELANOMA CANCER AMIDES Design and synthesis of new 2-anilinoquinolines bearing N-methylpicolinamide moiety as potential antiproliferative agents Article 10.1111/cbdd.12836 1 CHEMICAL BIOLOGY & DRUG DESIGN, v.89, no.1, pp.98 - 113 CHEMICAL BIOLOGY & DRUG DESIGN 89 1 98 113 scie scopus 000390354100009 2-s2.0-84987625478 Biochemistry & Molecular Biology Chemistry, Medicinal Biochemistry & Molecular Biology Pharmacology & Pharmacy Article RAF KINASE INHIBITORS ADVANCED HEPATOCELLULAR-CARCINOMA MULTIKINASE INHIBITOR BRAF INHIBITORS B-RAF SORAFENIB DISCOVERY MELANOMA CANCER AMIDES 2-anilinoquinoline antiproliferative activity N-methylpicolinamide RAF kinase