Abdel-Maksoud, Mohammed S. Ammar, Usama M. El-Gamal, Mohammed I. El-Din, Mahmoud M. Gamal Mersal, Karim I. Ali, Eslam M. H. Yoo, Kyung Ho Lee, Kyung-Tae Oh, Chang-Hyun 2024-01-19T18:33:02Z 2024-01-19T18:33:02Z 2022-01-25 2019-12 0045-2068 https://pubs.kist.re.kr/handle/201004/119226 In the present work, a novel series of B-RAF kinase inhibitors having imidazo[2,1-b]oxazole scaffold was designed and synthesized based on the structures of the well-known B-RAF inhibitors. The twenty two final compounds were tested over A375 and SKMEL28 cell lines to determine the primary cytotoxic activity of these compounds, and their activities were compared with that of sorafenib as a standard. Compounds 11c, 11e, 11o, 11q, 11r, and 11u exhibited higher cellular activity compared to sorafenib with IC50 values of 7.25, 8.03, 9.81, 8.47, 4.70, and 9.04 mu M, respectively and 10.38 mu M for sorafenib. In addition, the target compounds were screened for their anticancer activity by the NCI-60 cell line assay. Compounds 11v and 11u were the most active compounds with percent inhibition reached 95.99% for 11v and 87.03% for 11u over K562 cell line at 10 mu M concentration. Compound 11v was selected for 5-dose test mode. Furthermore, the kinase inhibitory activities of 11a, 11c, 11e, 11i, 11o, 11q, 11r, 11u, and 11v were determined against wild-type B-RAF, V600E-B-RAF, and RAF1. Compound 11o was the most potent against V600E-B-RAF with IC50 34 nM followed by 11q and 11u with IC50 92 and 93 nM, respectively. English ACADEMIC PRESS INC ELSEVIER SCIENCE Design, synthesis, and anticancer activity of imidazo[2,1-b]oxazole-based RAF kinase inhibitors Article 10.1016/j.bioorg.2019.103349 1 BIOORGANIC CHEMISTRY, v.93 BIOORGANIC CHEMISTRY 93 N scie scopus 000499717000059 2-s2.0-85073238456 Biochemistry & Molecular Biology Chemistry, Organic Biochemistry & Molecular Biology Chemistry Article AZOLE COMPOUNDS BRAF GENE DERIVATIVES MUTATIONS CANCER IDENTIFICATION PROGRESS DOCKING Anticancer B-RAF inhibitors Imidazo[2,1-b]oxazole Kinase inhibitor SAR