Discovery of a Series of Theophylline Derivatives Containing 1,2,3-Triazole for Treatment of Non-Small Cell Lung Cancer
Chemotherapy is the most common clinical treatment for non-small cell lung cancer (NSCLC), but low efficiency and high toxicity of current chemotherapy drugs limit their clinical application. Therefore, it is urgent to develop hypotoxic and efficient chemotherapy drugs. Theophylline, a natural compo...
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| Format: | Article |
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Frontiers Media S.A.
2021-10-01
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| Series: | Frontiers in Pharmacology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fphar.2021.753676/full |
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| author | Jiahui Ye Longfei Mao Luoyijun Xie Rongjun Zhang Yulin Liu Lizeng Peng Jianxue Yang Qingjiao Li Miaomiao Yuan |
| author_facet | Jiahui Ye Longfei Mao Luoyijun Xie Rongjun Zhang Yulin Liu Lizeng Peng Jianxue Yang Qingjiao Li Miaomiao Yuan |
| author_sort | Jiahui Ye |
| collection | DOAJ |
| description | Chemotherapy is the most common clinical treatment for non-small cell lung cancer (NSCLC), but low efficiency and high toxicity of current chemotherapy drugs limit their clinical application. Therefore, it is urgent to develop hypotoxic and efficient chemotherapy drugs. Theophylline, a natural compound, is safe and easy to get, and it can be used as a modified scaffold structure and hold huge potential for developing safe and efficient antitumor drugs. Herein, we linked theophylline with different azide compounds to synthesize a new type of 1,2,3-triazole ring-containing theophylline derivatives. We found that some theophylline1,2,3-triazole compounds showed a good tumor-suppressive efficacy. Especially, derivative d17 showed strong antiproliferative activity against a variety of cancer cells in vitro, including H460, A549, A2780, LOVO, MB-231, MCF-7, OVCAR3, SW480, and PC-9. It is worth noting that the two NSCLC cell lines H460 H and A549 are sensitive to compound d17 particularly, with IC50 of 5.929 ± 0.97 μM and 6.76 ± 0.25 μM, respectively. Compound d17 can significantly induce cell apoptosis by increasing the ratio of apoptotic protein Bax/Bcl-2 by downregulating the expression of phosphorylated Akt protein, and it has little toxicity to normal hepatocyte cells LO2 at therapeutic concentrations. These data indicate that these theophylline acetic acid-1,2,3-triazole derivatives may be potential drug candidates for anti-NSCLC and are worthy of further study. |
| first_indexed | 2024-12-16T07:55:13Z |
| format | Article |
| id | doaj.art-e8d715790ed646efa7599b1df7e83001 |
| institution | Directory Open Access Journal |
| issn | 1663-9812 |
| language | English |
| last_indexed | 2024-12-16T07:55:13Z |
| publishDate | 2021-10-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Pharmacology |
| spelling | doaj.art-e8d715790ed646efa7599b1df7e830012022-12-21T22:38:45ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122021-10-011210.3389/fphar.2021.753676753676Discovery of a Series of Theophylline Derivatives Containing 1,2,3-Triazole for Treatment of Non-Small Cell Lung CancerJiahui Ye0Longfei Mao1Luoyijun Xie2Rongjun Zhang3Yulin Liu4Lizeng Peng5Jianxue Yang6Qingjiao Li7Miaomiao Yuan8The Eighth Affiliated Hospital, Sun Yat-sen University, Shenzhen, ChinaSchool of Chemistry and Chemical Engineering, Henan Engineering Research Center of Chiral Hydroxyl Pharmaceutical, Henan Normal University, Xinxiang, ChinaThe Eighth Affiliated Hospital, Sun Yat-sen University, Shenzhen, ChinaThe Eighth Affiliated Hospital, Sun Yat-sen University, Shenzhen, ChinaThe Eighth Affiliated Hospital, Sun Yat-sen University, Shenzhen, ChinaInstitute of Agro-Food Science and Technology Shandong Academy of Agricultural Sciences, Key Laboratory of Agro-Products Processing Technology of Shandong Province, Key Laboratory of Novel Food Resources Processing Ministry of Agriculture, Jinan, ChinaDepartment of Neurology, The First Affiliated Hospital of Henan University of Science and Technology, Luoyang, ChinaThe Eighth Affiliated Hospital, Sun Yat-sen University, Shenzhen, ChinaThe Eighth Affiliated Hospital, Sun Yat-sen University, Shenzhen, ChinaChemotherapy is the most common clinical treatment for non-small cell lung cancer (NSCLC), but low efficiency and high toxicity of current chemotherapy drugs limit their clinical application. Therefore, it is urgent to develop hypotoxic and efficient chemotherapy drugs. Theophylline, a natural compound, is safe and easy to get, and it can be used as a modified scaffold structure and hold huge potential for developing safe and efficient antitumor drugs. Herein, we linked theophylline with different azide compounds to synthesize a new type of 1,2,3-triazole ring-containing theophylline derivatives. We found that some theophylline1,2,3-triazole compounds showed a good tumor-suppressive efficacy. Especially, derivative d17 showed strong antiproliferative activity against a variety of cancer cells in vitro, including H460, A549, A2780, LOVO, MB-231, MCF-7, OVCAR3, SW480, and PC-9. It is worth noting that the two NSCLC cell lines H460 H and A549 are sensitive to compound d17 particularly, with IC50 of 5.929 ± 0.97 μM and 6.76 ± 0.25 μM, respectively. Compound d17 can significantly induce cell apoptosis by increasing the ratio of apoptotic protein Bax/Bcl-2 by downregulating the expression of phosphorylated Akt protein, and it has little toxicity to normal hepatocyte cells LO2 at therapeutic concentrations. These data indicate that these theophylline acetic acid-1,2,3-triazole derivatives may be potential drug candidates for anti-NSCLC and are worthy of further study.https://www.frontiersin.org/articles/10.3389/fphar.2021.753676/fulltheophylline1,2,3-triazoleapoptosisNSCLCantitumor |
| spellingShingle | Jiahui Ye Longfei Mao Luoyijun Xie Rongjun Zhang Yulin Liu Lizeng Peng Jianxue Yang Qingjiao Li Miaomiao Yuan Discovery of a Series of Theophylline Derivatives Containing 1,2,3-Triazole for Treatment of Non-Small Cell Lung Cancer Frontiers in Pharmacology theophylline 1,2,3-triazole apoptosis NSCLC antitumor |
| title | Discovery of a Series of Theophylline Derivatives Containing 1,2,3-Triazole for Treatment of Non-Small Cell Lung Cancer |
| title_full | Discovery of a Series of Theophylline Derivatives Containing 1,2,3-Triazole for Treatment of Non-Small Cell Lung Cancer |
| title_fullStr | Discovery of a Series of Theophylline Derivatives Containing 1,2,3-Triazole for Treatment of Non-Small Cell Lung Cancer |
| title_full_unstemmed | Discovery of a Series of Theophylline Derivatives Containing 1,2,3-Triazole for Treatment of Non-Small Cell Lung Cancer |
| title_short | Discovery of a Series of Theophylline Derivatives Containing 1,2,3-Triazole for Treatment of Non-Small Cell Lung Cancer |
| title_sort | discovery of a series of theophylline derivatives containing 1 2 3 triazole for treatment of non small cell lung cancer |
| topic | theophylline 1,2,3-triazole apoptosis NSCLC antitumor |
| url | https://www.frontiersin.org/articles/10.3389/fphar.2021.753676/full |
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