2. Academic Validation
  3. Design, synthesis and anti-cancer activity of novel 1,2,3-triazole hybrids of erlotinib against cervical cancer via MAPK signaling pathway

Design, synthesis and anti-cancer activity of novel 1,2,3-triazole hybrids of erlotinib against cervical cancer via MAPK signaling pathway

  • Sci Rep. 2025 Jul 9;15(1):24582. doi: 10.1038/s41598-025-09168-8.
Lan Wang 1 2,  Xixi Hou 3,  Mengmeng Huang 1,  Baoyu He 4,  Longfei Mao 1 5,  Zhengwei Hu 2,  Ling Li 5,  Jingjing Guo 4,  Lizeng Peng 6
Affiliations

Affiliations

  • 1 College of Basic Medicine and Forensic Medicine, Henan University of Science and Technology, 263 Kaiyuan Road, Luoyang, 471000, China.
  • 2 Henan Jiante Biotechnology Group Co., Ltd, No. 6 Huaxia Road, High-tech Development Zone, Luoyang, 471000, China.
  • 3 The First Affiliated Hospital, College of Clinical Medicine of Henan, University of Science and Technology, Luoyang, 471000, China. lucyfly881104@163.com.
  • 4 Centre for Artificial Intelligence Driven Drug Discovery, Faculty of Applied Sciences, Macao Polytechnic University, Macao, China.
  • 5 Henan Jiahekang Biological Food Technology Co., Ltd., Luoyang, 471000, China.
  • 6 Key Laboratory of Novel Food Resources Processing Ministry of Agriculture, Key Laboratory of Agro-Products Processing Technology of Shandong Province, Institute of Agro-Food Science and Technology, Shandong Academy of Agricultural Sciences, Jinan, 250100, China. penglizeng@sdnu.edu.cn.
PMID: 40628949 DOI: 10.1038/s41598-025-09168-8
Abstract

Cervical Cancer, a common malignant tumor of the female reproductive system, ranks fourth in incidence and mortality among female cancers globally, which highlights the urgent need for new therapeutic agents to improve treatment outcomes. In this study, 16 new erlotinib-1,2,3-triazole derivatives were synthesized via click chemistry and evaluated for their anti-proliferative activities against HeLa cells using the MTT assay. Compound 3h exhibited the most potent antitumor activity, with a half-maximal inhibitory concentration (IC50) value of 1.35 ± 0.74 µM, significantly lower than that of erlotinib (IC50 = 25.91 ± 1.35 µM). Further assays showed that compound 3h reduced cell viability, inhibited colony formation, and suppressed migration. It arrested the cell cycle at the G2/M phase and induced mitochondrial Apoptosis, marked by decreased Bcl-2, increased Bax, and downregulated Caspase-9, Caspase-3, and PARP-1. Additionally, compound 3h promoted ROS accumulation, induced γ-H2AX expression, and regulated the phosphorylation of ERK, JNK, and p38. Molecular docking studies suggested direct binding to these MAPKs. Overall, compound 3h inhibited HeLa cell proliferation by inducing ROS-mediated DNA damage and mitochondrial Apoptosis via the MAPK pathway. This study provides evidence for the therapeutic potential of erlotinib-1,2,3-triazole derivatives in cervical Cancer treatment, offering new strategies for developing effective and low-toxicity drugs.

Keywords

Apoptosis; Cervical cancer; Erlotinib; MAPK signaling pathway; Triazole.

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