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Design, synthesis, and anticancer activity of imidazo[2,1-b]oxazole-based RAF kinase inhibitors

Abdel-Maksoud, Mohammed S.; Ammar, Usama M.; El-Gamal, Mohammed I.; Gamal El-Din, Mahmoud M.; Mersal, Karim I.; Ali, Eslam M.H.; Yoo, Kyung Ho; Lee, Kyung-Tae; Oh, Chang-Hyun


Mohammed S. Abdel-Maksoud

Mohammed I. El-Gamal

Mahmoud M. Gamal El-Din

Karim I. Mersal

Eslam M.H. Ali

Kyung Ho Yoo

Kyung-Tae Lee

Chang-Hyun Oh


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 IC 50 values of 7.25, 8.03, 9.81, 8.47, 4.70, and 9.04 µM, respectively and 10.38 µM 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 µM 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 IC 50 34 nM followed by 11q and 11u with IC 50 92 and 93 nM, respectively.

Journal Article Type Article
Acceptance Date Oct 5, 2019
Online Publication Date Oct 10, 2019
Publication Date 2019-12
Deposit Date Dec 11, 2022
Journal Bioorganic Chemistry
Print ISSN 0045-2068
Publisher Elsevier
Peer Reviewed Peer Reviewed
Volume 93
Article Number 103349
Keywords Anticancer, B-RAF inhibitors, Imidazo[2,1-b]oxazole, Kinase inhibitor, SAR
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