2. Academic Validation
  3. Development of Antitumor Drugs Targeting c-MYC Pu27 and KRAS G-Quadruplexes

Development of Antitumor Drugs Targeting c-MYC Pu27 and KRAS G-Quadruplexes

  • J Med Chem. 2025 Jul 24;68(14):14223-14238. doi: 10.1021/acs.jmedchem.3c00955.
Hany I Mohamed 1 2 3,  Zibing Song 4,  Yi He 1,  Chao Gao 1
Affiliations

Affiliations

  • 1 National R&D Center for Se-rich Agricultural Products Processing, Hubei Engineering Research Center for Deep Processing of Green Se-rich Agricultural Products, School of Modern Industry for Selenium Science and Engineering, Wuhan Polytechnic University, Wuhan, Hubei 430023, China.
  • 2 State Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine; Hubei Hongshan Laboratory; Interdisciplinary Sciences Institute; National Reference Laboratory of Veterinary Drug Residues (HZAU) and MAO Key Laboratory for Detection of Veterinary Drug Residues, Huazhong Agricultural University, Wuhan, Hubei 430070, China.
  • 3 Chemistry Department, Faculty of Science, Benha University, Benha 13518, Egypt.
  • 4 College of Chemistry, Huazhong Agricultural University, Wuhan, Hubei 430070, China.
PMID: 40651011 DOI: 10.1021/acs.jmedchem.3c00955
Abstract

Traditional chemotherapy remains the main treatment option for Cancer. However, drugs discovered through conventional targets are often accompanied by side effects and drug resistance, so more effective treatment options are urgently needed. Discovery of antitumor drugs targeting G-quadruplexes is an effective pathway. Here, a novel series of pyrazolo[4,3-c]quinolines as potential stabilizing ligands for c-Myc Pu27 and KRAS G-quadruplexes was synthesized. Compound PQ32 was observed to stabilize these G-quadruplexes with high ΔTm values. Biological investigations indicated that PQ32 inhibited tumor cell proliferation with an IC50 of ∼ 1.00 μM, arrested the cell cycle in the G2 phase, and caused cell Apoptosis. Further studies revealed that PQ32 could inhibit the expression of c-Myc and KRAS genes. Xenograft animal model assay suggested that PQ32 effectively inhibited the tumor growth in mice with comparable activity to cisplatin. Thus, the interaction of quinoline-based ligands with multiple G-quadruplex DNA provides a promising target for Anticancer therapeutic strategy.

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