Synthesis and In Vitro Antitumor Activity Evaluation of Gefitinib-1,2,3-Triazole Derivatives
In this study, 14 structurally novel gefitinib-1,2,3-triazole derivatives were synthesized using a click chemistry approach and characterized by <sup>1</sup>H NMR, <sup>13</sup>C NMR and high-resolution mass spectrometry (HRMS). Preliminary cell counting kit-8 results showed...
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MDPI AG
2024-02-01
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| author | Zijun Liu Jiancheng Liu En Gao Longfei Mao Shu Hu Sanqiang Li |
| author_facet | Zijun Liu Jiancheng Liu En Gao Longfei Mao Shu Hu Sanqiang Li |
| author_sort | Zijun Liu |
| collection | DOAJ |
| description | In this study, 14 structurally novel gefitinib-1,2,3-triazole derivatives were synthesized using a click chemistry approach and characterized by <sup>1</sup>H NMR, <sup>13</sup>C NMR and high-resolution mass spectrometry (HRMS). Preliminary cell counting kit-8 results showed that most of the compounds exhibit excellent antitumor activity against epidermal growth factor receptor wild-type lung cancer cells NCI-H1299, A549 and NCI-H1437. Among them, <b>4b</b> and <b>4c</b> showed the most prominent inhibitory effects. The half maximal inhibitory concentration (IC<sub>50</sub>) values of <b>4b</b> were 4.42 ± 0.24 μM (NCI-H1299), 3.94 ± 0.01 μM (A549) and 1.56 ± 0.06 μM (NCI-1437). The IC<sub>50</sub> values of <b>4c</b> were 4.60 ± 0.18 µM (NCI-H1299), 4.00 ± 0.08 μM (A549) and 3.51 ± 0.05 μM (NCI-H1437). Furthermore, our results showed that <b>4b</b> and <b>4c</b> could effectively inhibit proliferation, colony formation and cell migration in a concentration-dependent manner, as well as induce apoptosis in H1299 cells. In addition, <b>4b</b> and <b>4c</b> exerted its anti-tumor effects by inducing cell apoptosis, upregulating the expression of cleaved-caspase 3 and cleaved-PARP and downregulating the protein levels of Bcl-2. Based on these results, it is suggested that <b>4b</b> and <b>4c</b> be developed as potential new drugs for lung cancer treatment. |
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| spelling | doaj.art-d60f5bbbcfb943da855ee99248707f362024-02-23T15:29:02ZengMDPI AGMolecules1420-30492024-02-0129483710.3390/molecules29040837Synthesis and In Vitro Antitumor Activity Evaluation of Gefitinib-1,2,3-Triazole DerivativesZijun Liu0Jiancheng Liu1En Gao2Longfei Mao3Shu Hu4Sanqiang Li5College of Basic Medicine and Forensic Medicine, Henan University of Science and Technology, Luoyang 471023, ChinaCollege of Basic Medicine and Forensic Medicine, Henan University of Science and Technology, Luoyang 471023, ChinaSchool of Chemistry and Chemical Engineering, Henan Normal University, Xinxiang 453007, ChinaCollege of Basic Medicine and Forensic Medicine, Henan University of Science and Technology, Luoyang 471023, ChinaCollege of Basic Medicine and Forensic Medicine, Henan University of Science and Technology, Luoyang 471023, ChinaCollege of Basic Medicine and Forensic Medicine, Henan University of Science and Technology, Luoyang 471023, ChinaIn this study, 14 structurally novel gefitinib-1,2,3-triazole derivatives were synthesized using a click chemistry approach and characterized by <sup>1</sup>H NMR, <sup>13</sup>C NMR and high-resolution mass spectrometry (HRMS). Preliminary cell counting kit-8 results showed that most of the compounds exhibit excellent antitumor activity against epidermal growth factor receptor wild-type lung cancer cells NCI-H1299, A549 and NCI-H1437. Among them, <b>4b</b> and <b>4c</b> showed the most prominent inhibitory effects. The half maximal inhibitory concentration (IC<sub>50</sub>) values of <b>4b</b> were 4.42 ± 0.24 μM (NCI-H1299), 3.94 ± 0.01 μM (A549) and 1.56 ± 0.06 μM (NCI-1437). The IC<sub>50</sub> values of <b>4c</b> were 4.60 ± 0.18 µM (NCI-H1299), 4.00 ± 0.08 μM (A549) and 3.51 ± 0.05 μM (NCI-H1437). Furthermore, our results showed that <b>4b</b> and <b>4c</b> could effectively inhibit proliferation, colony formation and cell migration in a concentration-dependent manner, as well as induce apoptosis in H1299 cells. In addition, <b>4b</b> and <b>4c</b> exerted its anti-tumor effects by inducing cell apoptosis, upregulating the expression of cleaved-caspase 3 and cleaved-PARP and downregulating the protein levels of Bcl-2. Based on these results, it is suggested that <b>4b</b> and <b>4c</b> be developed as potential new drugs for lung cancer treatment.https://www.mdpi.com/1420-3049/29/4/837gefitinib1,2,3-triazoleantitumor drugcell apoptosiscell migration |
| spellingShingle | Zijun Liu Jiancheng Liu En Gao Longfei Mao Shu Hu Sanqiang Li Synthesis and In Vitro Antitumor Activity Evaluation of Gefitinib-1,2,3-Triazole Derivatives Molecules gefitinib 1,2,3-triazole antitumor drug cell apoptosis cell migration |
| title | Synthesis and In Vitro Antitumor Activity Evaluation of Gefitinib-1,2,3-Triazole Derivatives |
| title_full | Synthesis and In Vitro Antitumor Activity Evaluation of Gefitinib-1,2,3-Triazole Derivatives |
| title_fullStr | Synthesis and In Vitro Antitumor Activity Evaluation of Gefitinib-1,2,3-Triazole Derivatives |
| title_full_unstemmed | Synthesis and In Vitro Antitumor Activity Evaluation of Gefitinib-1,2,3-Triazole Derivatives |
| title_short | Synthesis and In Vitro Antitumor Activity Evaluation of Gefitinib-1,2,3-Triazole Derivatives |
| title_sort | synthesis and in vitro antitumor activity evaluation of gefitinib 1 2 3 triazole derivatives |
| topic | gefitinib 1,2,3-triazole antitumor drug cell apoptosis cell migration |
| url | https://www.mdpi.com/1420-3049/29/4/837 |
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