Discovery of New Quinolone-Based Diarylamides as Potent B-RAF^V600E/C-RAF Kinase Inhibitors Endowed with Promising In Vitro Anticancer Activity.

ABSTRACT: The emergence of cancer resistance to targeted therapy represents a significant challenge in cancer treatment. Therefore, identifying new anticancer candidates, particularly those addressing oncogenic mutants, is an urgent medical demand. A campaign of structural modifications has been conducted to further optimize our previously reported 2-anilinoquinoline-diarylamides conjugate VII as a B-RAFV600E/C-RAF inhibitor. Considering the incorporation of a methylene bridge between the terminal phenyl and cyclic diamine, focused quinoline-based arylamides have been tailored, synthesized, and biologically evaluated. Among them, the 5/6-hydroxyquinolines 17b and 18a stood out as the most potent members, with IC₅₀ values of 0.128 µM, 0.114 µM against B-RAF^V600E, a

SUBMITTER: Kim HJ 

PROVIDER: S-EPMC9963398 | biostudies-literature | 2023 Feb

REPOSITORIES: biostudies-literature