Design, synthesis and anti-cancer activity of novel 1,2,3-triazole hybrids of erlotinib against cervical cancer via MAPK signaling pathway
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 deriv...
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Nature Portfolio
2025-07-01
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| Online Access: | https://doi.org/10.1038/s41598-025-09168-8 |
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| author | Lan Wang Xixi Hou Mengmeng Huang Baoyu He Longfei Mao Zhengwei Hu Ling Li Jingjing Guo Lizeng Peng |
| author_facet | Lan Wang Xixi Hou Mengmeng Huang Baoyu He Longfei Mao Zhengwei Hu Ling Li Jingjing Guo Lizeng Peng |
| author_sort | Lan Wang |
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| description | 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. |
| format | Article |
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| institution | Kabale University |
| issn | 2045-2322 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Nature Portfolio |
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| spelling | doaj-art-3fa5be4a324a4b46a824ca41b6fdfefc2025-08-20T03:45:48ZengNature PortfolioScientific Reports2045-23222025-07-0115111310.1038/s41598-025-09168-8Design, synthesis and anti-cancer activity of novel 1,2,3-triazole hybrids of erlotinib against cervical cancer via MAPK signaling pathwayLan Wang0Xixi Hou1Mengmeng Huang2Baoyu He3Longfei Mao4Zhengwei Hu5Ling Li6Jingjing Guo7Lizeng Peng8College of Basic Medicine and Forensic Medicine, Henan University of Science and TechnologyThe First Affiliated Hospital, College of Clinical Medicine of Henan, University of Science and TechnologyCollege of Basic Medicine and Forensic Medicine, Henan University of Science and TechnologyCentre for Artificial Intelligence Driven Drug Discovery, Faculty of Applied Sciences, Macao Polytechnic UniversityCollege of Basic Medicine and Forensic Medicine, Henan University of Science and TechnologyHenan Jiante Biotechnology Group Co., LtdHenan Jiahekang Biological Food Technology Co., Ltd.Centre for Artificial Intelligence Driven Drug Discovery, Faculty of Applied Sciences, Macao Polytechnic UniversityKey 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 SciencesAbstract 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.https://doi.org/10.1038/s41598-025-09168-8Cervical cancerErlotinibTriazoleApoptosisMAPK signaling pathway |
| spellingShingle | Lan Wang Xixi Hou Mengmeng Huang Baoyu He Longfei Mao Zhengwei Hu Ling Li Jingjing Guo Lizeng Peng Design, synthesis and anti-cancer activity of novel 1,2,3-triazole hybrids of erlotinib against cervical cancer via MAPK signaling pathway Scientific Reports Cervical cancer Erlotinib Triazole Apoptosis MAPK signaling pathway |
| title | Design, synthesis and anti-cancer activity of novel 1,2,3-triazole hybrids of erlotinib against cervical cancer via MAPK signaling pathway |
| title_full | Design, synthesis and anti-cancer activity of novel 1,2,3-triazole hybrids of erlotinib against cervical cancer via MAPK signaling pathway |
| title_fullStr | Design, synthesis and anti-cancer activity of novel 1,2,3-triazole hybrids of erlotinib against cervical cancer via MAPK signaling pathway |
| title_full_unstemmed | Design, synthesis and anti-cancer activity of novel 1,2,3-triazole hybrids of erlotinib against cervical cancer via MAPK signaling pathway |
| title_short | Design, synthesis and anti-cancer activity of novel 1,2,3-triazole hybrids of erlotinib against cervical cancer via MAPK signaling pathway |
| title_sort | design synthesis and anti cancer activity of novel 1 2 3 triazole hybrids of erlotinib against cervical cancer via mapk signaling pathway |
| topic | Cervical cancer Erlotinib Triazole Apoptosis MAPK signaling pathway |
| url | https://doi.org/10.1038/s41598-025-09168-8 |
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