Synthesis of Novel Gefitinib-Conjugated 1,2,3-Triazole Derivatives and Their Effect of Inducing DNA Damage and Apoptosis in Tumor Cells
Compounds with rigid planar structures can insert into tumor cell DNA, thereby inducing DNA damage in tumor cells. In this study, quinazoline, a compound with a planar structure, was used as the core scaffold. A rigid planar 1,2,3-triazole moiety was introduced into its structure, and its activity w...
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MDPI AG
2024-11-01
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| Series: | Molecules |
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| Online Access: | https://www.mdpi.com/1420-3049/29/22/5438 |
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| author | Junfei Wu Xu Huang Shan Lu Ziyi Wang Longfei Mao Sanqiang Li |
| author_facet | Junfei Wu Xu Huang Shan Lu Ziyi Wang Longfei Mao Sanqiang Li |
| author_sort | Junfei Wu |
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| description | Compounds with rigid planar structures can insert into tumor cell DNA, thereby inducing DNA damage in tumor cells. In this study, quinazoline, a compound with a planar structure, was used as the core scaffold. A rigid planar 1,2,3-triazole moiety was introduced into its structure, and its activity was tested on HepG2 liver cancer cells. The results showed that most compounds exhibited inhibitory effects on HepG2 cells, and the IC50 values of the most effective compounds were 3.08 ± 0.37 μM and 3.60 ± 0.53 μM. We found that the designed compounds significantly upregulated the expression of γ-H2AX in tumor cells, inducing DNA damage while reducing PARP levels, thereby weakening the DNA damage repair capacity of tumor cells and leading to apoptosis. Additionally, these compounds inhibited the migration and invasion of HepG2 cells. One of the compounds was found to be low in toxicity in mice, suggesting its potential as a targeted DNA anti-tumor drug. |
| format | Article |
| id | doaj-art-a2b7df00346e42b1a67bf8e49eaa7a03 |
| institution | Kabale University |
| issn | 1420-3049 |
| language | English |
| publishDate | 2024-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj-art-a2b7df00346e42b1a67bf8e49eaa7a032024-11-26T18:16:01ZengMDPI AGMolecules1420-30492024-11-012922543810.3390/molecules29225438Synthesis of Novel Gefitinib-Conjugated 1,2,3-Triazole Derivatives and Their Effect of Inducing DNA Damage and Apoptosis in Tumor CellsJunfei Wu0Xu Huang1Shan Lu2Ziyi Wang3Longfei Mao4Sanqiang Li5College of Basic Medicine and Forensic Medicine, Henan University of Science and Technology, Luoyang 471003, ChinaCollege of Basic Medicine and Forensic Medicine, Henan University of Science and Technology, Luoyang 471003, ChinaCollege of Basic Medicine and Forensic Medicine, Henan University of Science and Technology, Luoyang 471003, ChinaCollege of Basic Medicine and Forensic Medicine, Henan University of Science and Technology, Luoyang 471003, ChinaCollege of Basic Medicine and Forensic Medicine, Henan University of Science and Technology, Luoyang 471003, ChinaCollege of Basic Medicine and Forensic Medicine, Henan University of Science and Technology, Luoyang 471003, ChinaCompounds with rigid planar structures can insert into tumor cell DNA, thereby inducing DNA damage in tumor cells. In this study, quinazoline, a compound with a planar structure, was used as the core scaffold. A rigid planar 1,2,3-triazole moiety was introduced into its structure, and its activity was tested on HepG2 liver cancer cells. The results showed that most compounds exhibited inhibitory effects on HepG2 cells, and the IC50 values of the most effective compounds were 3.08 ± 0.37 μM and 3.60 ± 0.53 μM. We found that the designed compounds significantly upregulated the expression of γ-H2AX in tumor cells, inducing DNA damage while reducing PARP levels, thereby weakening the DNA damage repair capacity of tumor cells and leading to apoptosis. Additionally, these compounds inhibited the migration and invasion of HepG2 cells. One of the compounds was found to be low in toxicity in mice, suggesting its potential as a targeted DNA anti-tumor drug.https://www.mdpi.com/1420-3049/29/22/5438rigid planar structuresquinazoline1,2,3-triazoleDNA damageHepG2 cells |
| spellingShingle | Junfei Wu Xu Huang Shan Lu Ziyi Wang Longfei Mao Sanqiang Li Synthesis of Novel Gefitinib-Conjugated 1,2,3-Triazole Derivatives and Their Effect of Inducing DNA Damage and Apoptosis in Tumor Cells Molecules rigid planar structures quinazoline 1,2,3-triazole DNA damage HepG2 cells |
| title | Synthesis of Novel Gefitinib-Conjugated 1,2,3-Triazole Derivatives and Their Effect of Inducing DNA Damage and Apoptosis in Tumor Cells |
| title_full | Synthesis of Novel Gefitinib-Conjugated 1,2,3-Triazole Derivatives and Their Effect of Inducing DNA Damage and Apoptosis in Tumor Cells |
| title_fullStr | Synthesis of Novel Gefitinib-Conjugated 1,2,3-Triazole Derivatives and Their Effect of Inducing DNA Damage and Apoptosis in Tumor Cells |
| title_full_unstemmed | Synthesis of Novel Gefitinib-Conjugated 1,2,3-Triazole Derivatives and Their Effect of Inducing DNA Damage and Apoptosis in Tumor Cells |
| title_short | Synthesis of Novel Gefitinib-Conjugated 1,2,3-Triazole Derivatives and Their Effect of Inducing DNA Damage and Apoptosis in Tumor Cells |
| title_sort | synthesis of novel gefitinib conjugated 1 2 3 triazole derivatives and their effect of inducing dna damage and apoptosis in tumor cells |
| topic | rigid planar structures quinazoline 1,2,3-triazole DNA damage HepG2 cells |
| url | https://www.mdpi.com/1420-3049/29/22/5438 |
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