Ali, Eslam M. H. Abdel-Maksoud, Mohammed S. Ammar, Usama M. Mersal, Karim, I Yoo, Kyung Ho Jooryeong, Park Oh, Chang-Hyun 2024-01-19T15:33:54Z 2024-01-19T15:33:54Z 2022-01-10 2021-01 0045-2068 https://pubs.kist.re.kr/handle/201004/117573 BRAF(V600E) mutation has been detected in various malignant tumours. Developing of potent BRAF(V600E) inhibitors is considered a leading step in the way to cure different cancer types. In the current work, a series of 38 4-(1Himidazol-5-yl)pyridin-2-amine derivatives was designed and synthesized using Dabrafenib as a lead compound for structural-guided optimization. The target compounds were evaluated as potential anticancer agents against NCI 60 human cancer cell lines. In 5-dose testing mode, two compounds 14h and 16e were tested to determine their IC50 values over each of the 60 cell lines. The selected candidates exhibited promising activity with mean IC(50 )values of 2.4 mu M and 3.6 mu M, respectively. Melanoma cancer cell lines exhibited the highest sensitivity after the treatment with the tested compounds 14h and 16e. The mean IC50 values of compounds 14h and 16e against Melanoma cancer cell lines are 1.8 mu M and 1.88 mu M, respectively. In addition, BRAF v600E kinase inhibitory activity was determined for each derivative. Compounds 15i, 15j, 16a, and 16d were the most potent inhibitors against BRAF(V600E)with IC50 76 nM, 32 nM, 35 nM, and 68 nM. The newly developed compounds represent a therapeutically promising approach for the treating various cancer types. English ACADEMIC PRESS INC ELSEVIER SCIENCE ANTIPROLIFERATIVE ACTIVITY B-RAF(V600E) INHIBITORS MULTIKINASE INHIBITOR C-RAF B-RAF BRAF KINASE MELANOMA CANCER DABRAFENIB Design, synthesis, and biological evaluation of novel imidazole derivatives possessing terminal sulphonamides as potential BRAF(V600E) inhibitors Article 10.1016/j.bioorg.2020.104508 1 BIOORGANIC CHEMISTRY, v.106 BIOORGANIC CHEMISTRY 106 scie scopus 000605009100006 2-s2.0-85097429858 Biochemistry & Molecular Biology Chemistry, Organic Biochemistry & Molecular Biology Chemistry Article ANTIPROLIFERATIVE ACTIVITY B-RAF(V600E) INHIBITORS MULTIKINASE INHIBITOR C-RAF B-RAF BRAF KINASE MELANOMA CANCER DABRAFENIB Protein kinase inhibitors BRAF(V600E) inhibitors Anticancer Imidazole SAR