Anti-Inflammatory Peroxidized Chlorahololide-Type Dimers Are Artifacts of Shizukaol-Type Dimers: From Phenomena Discovery and Confirmation to Potential Underlying Mechanism
In our research on naturally occurring sesquiterpenes, eight shizukaol-type dimers, one chlorahololide-type dimer, and one sarcanolide-type dimer were isolated from the roots of <i>Chloranthus fortunei.</i> As the project was implemented, we accidentally discovered that shizukaol-type di...
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MDPI AG
2024-02-01
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| author | Xiu-Wen Yin Ming Zhang Lan Wu Fu-Cai Ren Fu-Rong Yang Xiang-Dong Pu Zhi-Jun Zhang Chuan-Pu Shen |
| author_facet | Xiu-Wen Yin Ming Zhang Lan Wu Fu-Cai Ren Fu-Rong Yang Xiang-Dong Pu Zhi-Jun Zhang Chuan-Pu Shen |
| author_sort | Xiu-Wen Yin |
| collection | DOAJ |
| description | In our research on naturally occurring sesquiterpenes, eight shizukaol-type dimers, one chlorahololide-type dimer, and one sarcanolide-type dimer were isolated from the roots of <i>Chloranthus fortunei.</i> As the project was implemented, we accidentally discovered that shizukaol-type dimers can be converted into peroxidized chlorahololide-type dimers. This potential change was discovered after simulations of the changes in corresponding shizukaols showed that three peroxide products were generated (<b>1–3</b>), indicating that peroxidation reactions occurred. HPLC-HR-MS analysis results obtained for the shizukaol derivatives further demonstrate that the reaction occurred, and the type of substituent of small organic ester moieties at positions C-15’ and C-13’ of unit B were not decisively related to the reaction. Quantum chemical calculations of the mode dimer further demonstrated this phenomenon. The highest occupied molecular orbital (HOMO)–lowest unoccupied molecular orbital (LUMO) energy of the precursor and production revealed the advantageous yield of 4<i>β</i>-hydroperoxyl production. Additionally, the potential reaction mechanism was speculated and validated using the free energy in the reaction which successfully explained the feasibility of the reaction. Finally, the anti-inflammatory activity of the precursors and products was evaluated, and the products of peroxidation showed better anti-inflammatory activity. |
| first_indexed | 2024-03-07T22:19:54Z |
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| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-03-07T22:19:54Z |
| publishDate | 2024-02-01 |
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| spelling | doaj.art-78725e5b94474d2c9c00cfa63f434c732024-02-23T15:29:13ZengMDPI AGMolecules1420-30492024-02-0129490910.3390/molecules29040909Anti-Inflammatory Peroxidized Chlorahololide-Type Dimers Are Artifacts of Shizukaol-Type Dimers: From Phenomena Discovery and Confirmation to Potential Underlying MechanismXiu-Wen Yin0Ming Zhang1Lan Wu2Fu-Cai Ren3Fu-Rong Yang4Xiang-Dong Pu5Zhi-Jun Zhang6Chuan-Pu Shen7Anhui Provincial Laboratory of Inflammatory and Immunity Disease, Anhui Institute of Innovative Drugs, School of Pharmacy, Anhui Medical University, Hefei 230032, ChinaAnhui Provincial Laboratory of Inflammatory and Immunity Disease, Anhui Institute of Innovative Drugs, School of Pharmacy, Anhui Medical University, Hefei 230032, ChinaAnhui Provincial Laboratory of Inflammatory and Immunity Disease, Anhui Institute of Innovative Drugs, School of Pharmacy, Anhui Medical University, Hefei 230032, ChinaAnhui Provincial Laboratory of Inflammatory and Immunity Disease, Anhui Institute of Innovative Drugs, School of Pharmacy, Anhui Medical University, Hefei 230032, ChinaAnhui Provincial Laboratory of Inflammatory and Immunity Disease, Anhui Institute of Innovative Drugs, School of Pharmacy, Anhui Medical University, Hefei 230032, ChinaAnhui Provincial Laboratory of Inflammatory and Immunity Disease, Anhui Institute of Innovative Drugs, School of Pharmacy, Anhui Medical University, Hefei 230032, ChinaSchool of Pharmacy, Hubei University of Science and Technology, Xianning 437100, ChinaAnhui Provincial Laboratory of Inflammatory and Immunity Disease, Anhui Institute of Innovative Drugs, School of Pharmacy, Anhui Medical University, Hefei 230032, ChinaIn our research on naturally occurring sesquiterpenes, eight shizukaol-type dimers, one chlorahololide-type dimer, and one sarcanolide-type dimer were isolated from the roots of <i>Chloranthus fortunei.</i> As the project was implemented, we accidentally discovered that shizukaol-type dimers can be converted into peroxidized chlorahololide-type dimers. This potential change was discovered after simulations of the changes in corresponding shizukaols showed that three peroxide products were generated (<b>1–3</b>), indicating that peroxidation reactions occurred. HPLC-HR-MS analysis results obtained for the shizukaol derivatives further demonstrate that the reaction occurred, and the type of substituent of small organic ester moieties at positions C-15’ and C-13’ of unit B were not decisively related to the reaction. Quantum chemical calculations of the mode dimer further demonstrated this phenomenon. The highest occupied molecular orbital (HOMO)–lowest unoccupied molecular orbital (LUMO) energy of the precursor and production revealed the advantageous yield of 4<i>β</i>-hydroperoxyl production. Additionally, the potential reaction mechanism was speculated and validated using the free energy in the reaction which successfully explained the feasibility of the reaction. Finally, the anti-inflammatory activity of the precursors and products was evaluated, and the products of peroxidation showed better anti-inflammatory activity.https://www.mdpi.com/1420-3049/29/4/909<i>Chloranthus</i>sesquiterpene dimerstransformationquantum chemical calculationanti-inflammatory activity |
| spellingShingle | Xiu-Wen Yin Ming Zhang Lan Wu Fu-Cai Ren Fu-Rong Yang Xiang-Dong Pu Zhi-Jun Zhang Chuan-Pu Shen Anti-Inflammatory Peroxidized Chlorahololide-Type Dimers Are Artifacts of Shizukaol-Type Dimers: From Phenomena Discovery and Confirmation to Potential Underlying Mechanism Molecules <i>Chloranthus</i> sesquiterpene dimers transformation quantum chemical calculation anti-inflammatory activity |
| title | Anti-Inflammatory Peroxidized Chlorahololide-Type Dimers Are Artifacts of Shizukaol-Type Dimers: From Phenomena Discovery and Confirmation to Potential Underlying Mechanism |
| title_full | Anti-Inflammatory Peroxidized Chlorahololide-Type Dimers Are Artifacts of Shizukaol-Type Dimers: From Phenomena Discovery and Confirmation to Potential Underlying Mechanism |
| title_fullStr | Anti-Inflammatory Peroxidized Chlorahololide-Type Dimers Are Artifacts of Shizukaol-Type Dimers: From Phenomena Discovery and Confirmation to Potential Underlying Mechanism |
| title_full_unstemmed | Anti-Inflammatory Peroxidized Chlorahololide-Type Dimers Are Artifacts of Shizukaol-Type Dimers: From Phenomena Discovery and Confirmation to Potential Underlying Mechanism |
| title_short | Anti-Inflammatory Peroxidized Chlorahololide-Type Dimers Are Artifacts of Shizukaol-Type Dimers: From Phenomena Discovery and Confirmation to Potential Underlying Mechanism |
| title_sort | anti inflammatory peroxidized chlorahololide type dimers are artifacts of shizukaol type dimers from phenomena discovery and confirmation to potential underlying mechanism |
| topic | <i>Chloranthus</i> sesquiterpene dimers transformation quantum chemical calculation anti-inflammatory activity |
| url | https://www.mdpi.com/1420-3049/29/4/909 |
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