The Discovery of Novel Ferulic Acid Derivatives Incorporating Substituted Isopropanolamine Moieties as Potential Tobacco Mosaic Virus Helicase Inhibitors
Target-based drug design, a high-efficiency strategy used to guide the development of novel pesticide candidates, has attracted widespread attention. Herein, various natural-derived ferulic acid derivatives incorporating substituted isopropanolamine moieties were designed to target the tobacco mosai...
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| Format: | Article |
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MDPI AG
2022-11-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/23/22/13991 |
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| author | Zhenxing Li Binxin Yang Hongwu Liu Yue Ding Zimian Fang Wubin Shao Puying Qi Xiang Zhou Liwei Liu Song Yang |
| author_facet | Zhenxing Li Binxin Yang Hongwu Liu Yue Ding Zimian Fang Wubin Shao Puying Qi Xiang Zhou Liwei Liu Song Yang |
| author_sort | Zhenxing Li |
| collection | DOAJ |
| description | Target-based drug design, a high-efficiency strategy used to guide the development of novel pesticide candidates, has attracted widespread attention. Herein, various natural-derived ferulic acid derivatives incorporating substituted isopropanolamine moieties were designed to target the tobacco mosaic virus (TMV) helicase. Bioassays demonstrating the optimized <b>A<sub>19</sub></b>, <b>A<sub>20</sub></b>, <b>A<sub>29</sub></b>, and <b>A<sub>31</sub></b> displayed excellent in vivo antiviral curative abilities, affording corresponding EC<sub>50</sub> values of 251.1, 336.2, 347.1, and 385.5 μg/mL, which visibly surpassed those of commercial ribavirin (655.0 μg/mL). Moreover, configurational analysis shows that the <i>R</i>-forms of target compounds were more beneficial to aggrandize antiviral profiles. Mechanism studies indicate that <b><i>R</i>-A<sub>19</sub></b> had a strong affinity (<i>K</i><sub>d</sub> = 5.4 μM) to the TMV helicase and inhibited its ability to hydrolyze ATP (50.61% at 200 μM). Meanwhile, <b>A<sub>19</sub></b> could down-regulate the expression of the TMV helicase <i>gene</i> in the host to attenuate viral replication. These results illustrate the excellent inhibitory activity of <b>A<sub>19</sub></b> towards the TMV helicase. Additionally, docking simulations uncovered that <b><i>R</i>-A<sub>19</sub></b> formed more hydrogen bonds with the TMV helicase in the binding pocket. Recent studies have unambiguously manifested that these designed derivatives could be considered as promising potential helicase-based inhibitors for plant disease control. |
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| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-09T18:17:20Z |
| publishDate | 2022-11-01 |
| publisher | MDPI AG |
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| series | International Journal of Molecular Sciences |
| spelling | doaj.art-0e5292c27845439194a541cf5d2da00e2023-11-24T08:36:50ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-11-0123221399110.3390/ijms232213991The Discovery of Novel Ferulic Acid Derivatives Incorporating Substituted Isopropanolamine Moieties as Potential Tobacco Mosaic Virus Helicase InhibitorsZhenxing Li0Binxin Yang1Hongwu Liu2Yue Ding3Zimian Fang4Wubin Shao5Puying Qi6Xiang Zhou7Liwei Liu8Song Yang9State Key Laboratory Breeding Base of Green Pesticide and Agricultural Bioengineering, Key Laboratory of Green Pesticide and Agricultural Bioengineering, Ministry of Education, Center for R & D of Fine Chemicals, Guizhou University, Guiyang 550025, ChinaState Key Laboratory Breeding Base of Green Pesticide and Agricultural Bioengineering, Key Laboratory of Green Pesticide and Agricultural Bioengineering, Ministry of Education, Center for R & D of Fine Chemicals, Guizhou University, Guiyang 550025, ChinaState Key Laboratory Breeding Base of Green Pesticide and Agricultural Bioengineering, Key Laboratory of Green Pesticide and Agricultural Bioengineering, Ministry of Education, Center for R & D of Fine Chemicals, Guizhou University, Guiyang 550025, ChinaState Key Laboratory Breeding Base of Green Pesticide and Agricultural Bioengineering, Key Laboratory of Green Pesticide and Agricultural Bioengineering, Ministry of Education, Center for R & D of Fine Chemicals, Guizhou University, Guiyang 550025, ChinaState Key Laboratory Breeding Base of Green Pesticide and Agricultural Bioengineering, Key Laboratory of Green Pesticide and Agricultural Bioengineering, Ministry of Education, Center for R & D of Fine Chemicals, Guizhou University, Guiyang 550025, ChinaState Key Laboratory Breeding Base of Green Pesticide and Agricultural Bioengineering, Key Laboratory of Green Pesticide and Agricultural Bioengineering, Ministry of Education, Center for R & D of Fine Chemicals, Guizhou University, Guiyang 550025, ChinaState Key Laboratory Breeding Base of Green Pesticide and Agricultural Bioengineering, Key Laboratory of Green Pesticide and Agricultural Bioengineering, Ministry of Education, Center for R & D of Fine Chemicals, Guizhou University, Guiyang 550025, ChinaState Key Laboratory Breeding Base of Green Pesticide and Agricultural Bioengineering, Key Laboratory of Green Pesticide and Agricultural Bioengineering, Ministry of Education, Center for R & D of Fine Chemicals, Guizhou University, Guiyang 550025, ChinaState Key Laboratory Breeding Base of Green Pesticide and Agricultural Bioengineering, Key Laboratory of Green Pesticide and Agricultural Bioengineering, Ministry of Education, Center for R & D of Fine Chemicals, Guizhou University, Guiyang 550025, ChinaState Key Laboratory Breeding Base of Green Pesticide and Agricultural Bioengineering, Key Laboratory of Green Pesticide and Agricultural Bioengineering, Ministry of Education, Center for R & D of Fine Chemicals, Guizhou University, Guiyang 550025, ChinaTarget-based drug design, a high-efficiency strategy used to guide the development of novel pesticide candidates, has attracted widespread attention. Herein, various natural-derived ferulic acid derivatives incorporating substituted isopropanolamine moieties were designed to target the tobacco mosaic virus (TMV) helicase. Bioassays demonstrating the optimized <b>A<sub>19</sub></b>, <b>A<sub>20</sub></b>, <b>A<sub>29</sub></b>, and <b>A<sub>31</sub></b> displayed excellent in vivo antiviral curative abilities, affording corresponding EC<sub>50</sub> values of 251.1, 336.2, 347.1, and 385.5 μg/mL, which visibly surpassed those of commercial ribavirin (655.0 μg/mL). Moreover, configurational analysis shows that the <i>R</i>-forms of target compounds were more beneficial to aggrandize antiviral profiles. Mechanism studies indicate that <b><i>R</i>-A<sub>19</sub></b> had a strong affinity (<i>K</i><sub>d</sub> = 5.4 μM) to the TMV helicase and inhibited its ability to hydrolyze ATP (50.61% at 200 μM). Meanwhile, <b>A<sub>19</sub></b> could down-regulate the expression of the TMV helicase <i>gene</i> in the host to attenuate viral replication. These results illustrate the excellent inhibitory activity of <b>A<sub>19</sub></b> towards the TMV helicase. Additionally, docking simulations uncovered that <b><i>R</i>-A<sub>19</sub></b> formed more hydrogen bonds with the TMV helicase in the binding pocket. Recent studies have unambiguously manifested that these designed derivatives could be considered as promising potential helicase-based inhibitors for plant disease control.https://www.mdpi.com/1422-0067/23/22/13991ferulic acidantiviral assaymolecular dockinghelicaseinhibitor |
| spellingShingle | Zhenxing Li Binxin Yang Hongwu Liu Yue Ding Zimian Fang Wubin Shao Puying Qi Xiang Zhou Liwei Liu Song Yang The Discovery of Novel Ferulic Acid Derivatives Incorporating Substituted Isopropanolamine Moieties as Potential Tobacco Mosaic Virus Helicase Inhibitors International Journal of Molecular Sciences ferulic acid antiviral assay molecular docking helicase inhibitor |
| title | The Discovery of Novel Ferulic Acid Derivatives Incorporating Substituted Isopropanolamine Moieties as Potential Tobacco Mosaic Virus Helicase Inhibitors |
| title_full | The Discovery of Novel Ferulic Acid Derivatives Incorporating Substituted Isopropanolamine Moieties as Potential Tobacco Mosaic Virus Helicase Inhibitors |
| title_fullStr | The Discovery of Novel Ferulic Acid Derivatives Incorporating Substituted Isopropanolamine Moieties as Potential Tobacco Mosaic Virus Helicase Inhibitors |
| title_full_unstemmed | The Discovery of Novel Ferulic Acid Derivatives Incorporating Substituted Isopropanolamine Moieties as Potential Tobacco Mosaic Virus Helicase Inhibitors |
| title_short | The Discovery of Novel Ferulic Acid Derivatives Incorporating Substituted Isopropanolamine Moieties as Potential Tobacco Mosaic Virus Helicase Inhibitors |
| title_sort | discovery of novel ferulic acid derivatives incorporating substituted isopropanolamine moieties as potential tobacco mosaic virus helicase inhibitors |
| topic | ferulic acid antiviral assay molecular docking helicase inhibitor |
| url | https://www.mdpi.com/1422-0067/23/22/13991 |
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