2. Academic Validation
  3. Synthesis and biological evaluation of novel 4-Arylaminoquinolines derivatives as EGFR/HDAC inhibitors

Synthesis and biological evaluation of novel 4-Arylaminoquinolines derivatives as EGFR/HDAC inhibitors

  • Bioorg Med Chem Lett. 2025 Jul 1:122:130214. doi: 10.1016/j.bmcl.2025.130214.
Keke Yao 1,  Yaxin Li 2,  Wei Wei 1,  Sisi Liu 3,  Xiaoli Wang 1,  Jiamin Xu 1,  Ranran Zhang 3,  Zhigang Wu 3,  Chunyan Guo 3,  Leifu Yang 1,  Liming Hu 4
Affiliations

Affiliations

  • 1 College of Chemistry and Life Science, Beijing University of Technology, Beijing 100124, China.
  • 2 College of Chemistry and Life Science, Beijing University of Technology, Beijing 100124, China; Hebei Key Laboratory of Neuropharmacology, School of Pharmacy, Hebei North University, Zhangjiakou 075000, China.
  • 3 Hebei Key Laboratory of Neuropharmacology, School of Pharmacy, Hebei North University, Zhangjiakou 075000, China.
  • 4 College of Chemistry and Life Science, Beijing University of Technology, Beijing 100124, China; Beijing Key Laboratory of Environmental and Viral Oncology, Beijing University of Technology, Beijing 100124, China.
PMID: 40164393 DOI: 10.1016/j.bmcl.2025.130214
Abstract

Lung Cancer, particularly non-small cell lung Cancer (NSCLC), remains a leading cause of cancer-related mortality worldwide. Resistance to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) and the role of epigenetic modifications, such as histone deacetylation, in Cancer progression underscore the need for novel therapeutic strategies. This study reports the design, synthesis, and biological evaluation of novel 4-arylaminoquinoline derivatives as dual inhibitors targeting EGFR and histone deacetylase (HDAC). Leveraging structure-activity relationship insights, a series of compounds were synthesized by integrating pharmacophoric elements of EGFR-TKIs and HDAC inhibitors and their kinase and cellular activities were evaluated. Compound 22c2 exhibited the highest inhibitory activities against EGFR (IC50 = 4.81 nM) and HDAC (IC50 = 119.4 nM and 354.8 nM for HDAC1 and HDAC3, respectively). Moreover, 22c2 demonstrated excellent anti-proliferative effects on four human Cancer cell lines. These findings provide a foundation for developing dual EGFR/HDAC inhibitors as potential Anticancer therapeutics.

Keywords

Antitumor activity; Dual inhibitors; EGFR tyrosine kinase; HDAC.

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