Synthesis, evaluation, and computational chemistry of novel selenenyl sulfides as 3C protease inhibitors with strong cell-based antiviral activity
The 3C protease (3Cpro) is an important enzyme for developing therapeutic medicines against some severe viral infections. In order to discover new classes of antiviral agents, 42 novel selenenyl sulfides were prepared and characterized by 1H NMR, 13C NMR, 77Se NMR and HRMS. The target compounds demo...
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| Format: | Article |
| Language: | English |
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Elsevier
2024-04-01
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| Series: | Arabian Journal of Chemistry |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S1878535224001151 |
| _version_ | 1797248335382315008 |
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| author | Jin-Yin Tang Shengwang Dai Xiaofang Wang Mengting Zhang Jin-Rui Shi Yong-Xuan Hong Zhi-Juan Sun Huan-Qin Dai Jian-Guo Wang |
| author_facet | Jin-Yin Tang Shengwang Dai Xiaofang Wang Mengting Zhang Jin-Rui Shi Yong-Xuan Hong Zhi-Juan Sun Huan-Qin Dai Jian-Guo Wang |
| author_sort | Jin-Yin Tang |
| collection | DOAJ |
| description | The 3C protease (3Cpro) is an important enzyme for developing therapeutic medicines against some severe viral infections. In order to discover new classes of antiviral agents, 42 novel selenenyl sulfides were prepared and characterized by 1H NMR, 13C NMR, 77Se NMR and HRMS. The target compounds demonstrated promising inhibitions against 3Cpro from either enterovirus 71 (EV71) or coxsackievirus B3 (CVB3), as well as desirable cell-based antiviral activity against these viruses. Among them, 11f displayed the most potent IC50 value of 0.28 ± 0.05 μM against EV71-3Cpro, and the strongest IC50 value of 0.72 ± 0.15 μM against CVB3, with a selectivity index of 51.5 against Hela cell, superior to the control drug rupintrivir. In addition, molecular docking was undertaken to predict a possible binding mode for compound 11f, and a comparative molecular field analysis (CoMFA) model was subsequently generated to understand the structure-activity relationships. Overall, the present research has provided some new insights to design a distinct family of antiviral compounds. |
| first_indexed | 2024-04-24T20:12:57Z |
| format | Article |
| id | doaj.art-450bafbbac6d42ec834bc2f09ab79a4d |
| institution | Directory Open Access Journal |
| issn | 1878-5352 |
| language | English |
| last_indexed | 2024-04-24T20:12:57Z |
| publishDate | 2024-04-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Arabian Journal of Chemistry |
| spelling | doaj.art-450bafbbac6d42ec834bc2f09ab79a4d2024-03-23T06:23:46ZengElsevierArabian Journal of Chemistry1878-53522024-04-01174105713Synthesis, evaluation, and computational chemistry of novel selenenyl sulfides as 3C protease inhibitors with strong cell-based antiviral activityJin-Yin Tang0Shengwang Dai1Xiaofang Wang2Mengting Zhang3Jin-Rui Shi4Yong-Xuan Hong5Zhi-Juan Sun6Huan-Qin Dai7Jian-Guo Wang8State-Key Laboratory and Research Institute of Elemento-Organic Chemistry, Frontiers Science Center for New Organic Matter, National Engineering Research Center of Pesticide, College of Chemistry, Nankai University, Tianjin 300071, ChinaState Key Laboratory of Mycology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, ChinaNewish Biological R&D Center, Beijing 100176, ChinaState Key Laboratory of Mycology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, ChinaState-Key Laboratory and Research Institute of Elemento-Organic Chemistry, Frontiers Science Center for New Organic Matter, National Engineering Research Center of Pesticide, College of Chemistry, Nankai University, Tianjin 300071, ChinaState-Key Laboratory and Research Institute of Elemento-Organic Chemistry, Frontiers Science Center for New Organic Matter, National Engineering Research Center of Pesticide, College of Chemistry, Nankai University, Tianjin 300071, ChinaNewish Biological R&D Center, Beijing 100176, ChinaState Key Laboratory of Mycology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China; Savaid Medical School, University of Chinese Academy of Sciences, Beijing, 100049, China; Corresponding authors at: State Key Laboratory of Mycology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China (H.Q. Dai).State-Key Laboratory and Research Institute of Elemento-Organic Chemistry, Frontiers Science Center for New Organic Matter, National Engineering Research Center of Pesticide, College of Chemistry, Nankai University, Tianjin 300071, China; Corresponding authors at: State Key Laboratory of Mycology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China (H.Q. Dai).The 3C protease (3Cpro) is an important enzyme for developing therapeutic medicines against some severe viral infections. In order to discover new classes of antiviral agents, 42 novel selenenyl sulfides were prepared and characterized by 1H NMR, 13C NMR, 77Se NMR and HRMS. The target compounds demonstrated promising inhibitions against 3Cpro from either enterovirus 71 (EV71) or coxsackievirus B3 (CVB3), as well as desirable cell-based antiviral activity against these viruses. Among them, 11f displayed the most potent IC50 value of 0.28 ± 0.05 μM against EV71-3Cpro, and the strongest IC50 value of 0.72 ± 0.15 μM against CVB3, with a selectivity index of 51.5 against Hela cell, superior to the control drug rupintrivir. In addition, molecular docking was undertaken to predict a possible binding mode for compound 11f, and a comparative molecular field analysis (CoMFA) model was subsequently generated to understand the structure-activity relationships. Overall, the present research has provided some new insights to design a distinct family of antiviral compounds.http://www.sciencedirect.com/science/article/pii/S18785352240011513C proteaseSelenenyl sulfidesAntiviral activitySelectivity indexComputational chemistry |
| spellingShingle | Jin-Yin Tang Shengwang Dai Xiaofang Wang Mengting Zhang Jin-Rui Shi Yong-Xuan Hong Zhi-Juan Sun Huan-Qin Dai Jian-Guo Wang Synthesis, evaluation, and computational chemistry of novel selenenyl sulfides as 3C protease inhibitors with strong cell-based antiviral activity Arabian Journal of Chemistry 3C protease Selenenyl sulfides Antiviral activity Selectivity index Computational chemistry |
| title | Synthesis, evaluation, and computational chemistry of novel selenenyl sulfides as 3C protease inhibitors with strong cell-based antiviral activity |
| title_full | Synthesis, evaluation, and computational chemistry of novel selenenyl sulfides as 3C protease inhibitors with strong cell-based antiviral activity |
| title_fullStr | Synthesis, evaluation, and computational chemistry of novel selenenyl sulfides as 3C protease inhibitors with strong cell-based antiviral activity |
| title_full_unstemmed | Synthesis, evaluation, and computational chemistry of novel selenenyl sulfides as 3C protease inhibitors with strong cell-based antiviral activity |
| title_short | Synthesis, evaluation, and computational chemistry of novel selenenyl sulfides as 3C protease inhibitors with strong cell-based antiviral activity |
| title_sort | synthesis evaluation and computational chemistry of novel selenenyl sulfides as 3c protease inhibitors with strong cell based antiviral activity |
| topic | 3C protease Selenenyl sulfides Antiviral activity Selectivity index Computational chemistry |
| url | http://www.sciencedirect.com/science/article/pii/S1878535224001151 |
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