Research Output
Discovery of novel naphthalene-based diarylamides as pan-Raf kinase inhibitors with promising anti-melanoma activity: rational design, synthesis, in vitro and in silico screening
  Raf kinase enzymes are often dysregulated in melanoma. While sorafenib demonstrates strong activity against wild-type B-Raf, it fails to effectively inhibit the mutated form of B-Raf. In this study, sorafenib served as a lead compound for the development of new derivatives designed to enhance inhibitory activity across multiple Raf isoforms (pan-Raf inhibitors). Novel naphthalene-based diarylamide derivatives were subsequently designed, synthesized, and evaluated for their biological activity against various Raf kinase isoforms and the melanoma A375 cell line. Among these, compound 9a, containing a difluoromethoxy group, demonstrated strong inhibitory activity across B-RafWT, B-RafV600E, and c-Raf. Additionally, it induced G2/M phase arrest and triggered dose-dependent apoptosis, effectively suppressing both cell proliferation and survival. Compound 9a also exhibited high selectivity for Raf isoforms with minimal off-target effects, underscoring its specificity and therapeutic potential for Raf-driven malignancies.

  • Date:

    08 February 2025

  • Publication Status:

    Published

  • Publisher

    Springer Science and Business Media LLC

  • DOI:

    10.1007/s12272-025-01533-5

  • ISSN:

    0253-6269

  • Funders:

    New Funder

Citation

Elkamhawy, A., Ammar, U. M., Kim, M., Gul, A. R., Park, T. J., & Lee, K. (2025). Discovery of novel naphthalene-based diarylamides as pan-Raf kinase inhibitors with promising anti-melanoma activity: rational design, synthesis, in vitro and in silico screening. Archives of Pharmacal Research, 48(2), 150-165. https://doi.org/10.1007/s12272-025-01533-5

Authors

Keywords

Pan-Raf kinase inhibitors, Drug design, Naphthalene-based derivatives, Difuoromethoxy group, Anticancer drug, Melanoma

Monthly Views:

Available Documents