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Benzimidazole-Based Derivatives as Apoptotic Antiproliferative Agents: Design, Synthesis, Docking, and Mechanistic Studies.
- Source :
- Molecules; Jan2024, Vol. 29 Issue 2, p446, 28p
- Publication Year :
- 2024
-
Abstract
- A new class of benzimidazole-based derivatives (4a–j, 5, and 6) with potential dual inhibition of EGFR and BRAF<superscript>V600E</superscript> has been developed. The newly synthesized compounds were submitted for testing for antiproliferative activity against the NCI-60 cell line. All newly synthesized compounds 4a–j, 5, and 6 were selected for testing against a panel of sixty cancer cell lines at a single concentration of 10 µM. Some compounds tested demonstrated remarkable antiproliferative activity against the cell lines tested. Compounds 4c, 4e, and 4g were chosen for five-dose testing against 60 human tumor cell lines. Compound 4c demonstrated strong selectivity against the leukemia subpanel, with a selectivity ratio of 5.96 at the GI<subscript>50</subscript> level. The most effective in vitro anti-cancer assay derivatives (4c, 4d, 4e, 4g, and 4h) were tested for EGFR and BRAF<superscript>V600E</superscript> inhibition as potential targets for antiproliferative action. The results revealed that compounds 4c and 4e have significant antiproliferative activity as dual EGFR/BRAF<superscript>V600E</superscript> inhibitors. Compounds 4c and 4e induced apoptosis by increasing caspase-3, caspase-8, and Bax levels while decreasing the anti-apoptotic Bcl2 protein. Moreover, molecular docking studies confirmed the potential of compounds 4c and 4e to act as dual EGFR/BRAF<superscript>V600E</superscript> inhibitors. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 14203049
- Volume :
- 29
- Issue :
- 2
- Database :
- Complementary Index
- Journal :
- Molecules
- Publication Type :
- Academic Journal
- Accession number :
- 175079713
- Full Text :
- https://doi.org/10.3390/molecules29020446