Design, Synthesis, Antiproliferative Actions, and DFT Studies of New Bis-Pyrazoline Derivatives as Dual EGFR/BRAF^V600E Inhibitors.

ABSTRACT: Some new Bis-pyrazoline hybrids 8-17 with dual EGFR and BRAF^V600E inhibitors have been developed. The target compounds were synthesized and tested in vitro against four cancer cell lines. Compounds 12, 15, and 17 demonstrated strong antiproliferative activity with GI₅₀ values of 1.05 µM, 1.50 µM, and 1.20 µM, respectively. Hybrids showed dual inhibition of EGFR and BRAF^V600E. Compounds 12, 15, and 17 inhibited EGFR-like erlotinib and exhibited promising anticancer activity. Compound 12 is the most potent inhibitor of cancer cell proliferation and BRAF^V600E. Compounds 12 and 17 induced apoptosis by increasing caspase 3, 8, and Bax levels, and resulted in the downregulation of th

SUBMITTER: Al-Wahaibi LH 

PROVIDER: S-EPMC10218941 | biostudies-literature | 2023 May

REPOSITORIES: biostudies-literature