Design, Synthesis, and Anti-Inflammatory Activities of 12-Dehydropyxinol Derivatives
Pyxinol skeleton is a promising framework of anti-inflammatory agents formed in the human liver from 20<i>S</i>-protopanaxadiol, the main active aglycone of ginsenosides. In the present study, a new series of amino acid-containing derivatives were produced from 12-dehydropyxinol, a pyxin...
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MDPI AG
2023-01-01
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| author | Yunxiao Wang Xiaoliang Mi Yuan Du Shuang Li Liping Yu Meng Gao Xiaoyue Yang Zhihua Song Hui Yu Gangqiang Yang |
| author_facet | Yunxiao Wang Xiaoliang Mi Yuan Du Shuang Li Liping Yu Meng Gao Xiaoyue Yang Zhihua Song Hui Yu Gangqiang Yang |
| author_sort | Yunxiao Wang |
| collection | DOAJ |
| description | Pyxinol skeleton is a promising framework of anti-inflammatory agents formed in the human liver from 20<i>S</i>-protopanaxadiol, the main active aglycone of ginsenosides. In the present study, a new series of amino acid-containing derivatives were produced from 12-dehydropyxinol, a pyxinol oxidation metabolite, and its anti-inflammatory activity was assessed using an NO inhibition assay. Interestingly, the dehydrogenation at C-12 of pyxinol derivatives improved their potency greatly. Furthermore, half of the derivatives exhibited better NO inhibitory activity than hydrocortisone sodium succinate, a glucocorticoid drug. The structure–activity relationship analysis indicated that the kinds of amino acid residues and their hydrophilicity influenced the activity to a great extent, as did <i>R</i>/<i>S</i> stereochemistry at C-24. Of the various derivatives, <b>5c</b> with an <i>N</i>-Boc-protected phenylalanine residue showed the highest NO inhibitory activity and relatively low cytotoxicity. Moreover, derivative <b>5c</b> could dose-dependently suppress iNOS, IL-1β, and TNF-α via the MAPK and NF-κB pathways, but not the GR pathway. Overall, pyxinol derivatives hold potential for application as anti-inflammatory agents. |
| first_indexed | 2024-03-11T09:32:25Z |
| format | Article |
| id | doaj.art-73da20249e3b49c09aedded42bb4e241 |
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| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-03-11T09:32:25Z |
| publishDate | 2023-01-01 |
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| series | Molecules |
| spelling | doaj.art-73da20249e3b49c09aedded42bb4e2412023-11-16T17:30:36ZengMDPI AGMolecules1420-30492023-01-01283130710.3390/molecules28031307Design, Synthesis, and Anti-Inflammatory Activities of 12-Dehydropyxinol DerivativesYunxiao Wang0Xiaoliang Mi1Yuan Du2Shuang Li3Liping Yu4Meng Gao5Xiaoyue Yang6Zhihua Song7Hui Yu8Gangqiang Yang9School of Pharmacy, Collaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs in Universities of Shandong, Key Laboratory of Molecular Pharmacology and Drug Evaluation (Yantai University), Ministry of Education, Yantai University, Yantai 264005, ChinaSchool of Pharmacy, Collaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs in Universities of Shandong, Key Laboratory of Molecular Pharmacology and Drug Evaluation (Yantai University), Ministry of Education, Yantai University, Yantai 264005, ChinaSchool of Pharmacy, Collaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs in Universities of Shandong, Key Laboratory of Molecular Pharmacology and Drug Evaluation (Yantai University), Ministry of Education, Yantai University, Yantai 264005, ChinaSchool of Pharmacy, Collaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs in Universities of Shandong, Key Laboratory of Molecular Pharmacology and Drug Evaluation (Yantai University), Ministry of Education, Yantai University, Yantai 264005, ChinaSchool of Pharmacy, Collaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs in Universities of Shandong, Key Laboratory of Molecular Pharmacology and Drug Evaluation (Yantai University), Ministry of Education, Yantai University, Yantai 264005, ChinaSchool of Pharmacy, Collaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs in Universities of Shandong, Key Laboratory of Molecular Pharmacology and Drug Evaluation (Yantai University), Ministry of Education, Yantai University, Yantai 264005, ChinaSchool of Pharmacy, Collaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs in Universities of Shandong, Key Laboratory of Molecular Pharmacology and Drug Evaluation (Yantai University), Ministry of Education, Yantai University, Yantai 264005, ChinaSchool of Pharmacy, Collaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs in Universities of Shandong, Key Laboratory of Molecular Pharmacology and Drug Evaluation (Yantai University), Ministry of Education, Yantai University, Yantai 264005, ChinaCollege of Food Engineering, Ludong University, Yantai 264025, ChinaSchool of Pharmacy, Collaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs in Universities of Shandong, Key Laboratory of Molecular Pharmacology and Drug Evaluation (Yantai University), Ministry of Education, Yantai University, Yantai 264005, ChinaPyxinol skeleton is a promising framework of anti-inflammatory agents formed in the human liver from 20<i>S</i>-protopanaxadiol, the main active aglycone of ginsenosides. In the present study, a new series of amino acid-containing derivatives were produced from 12-dehydropyxinol, a pyxinol oxidation metabolite, and its anti-inflammatory activity was assessed using an NO inhibition assay. Interestingly, the dehydrogenation at C-12 of pyxinol derivatives improved their potency greatly. Furthermore, half of the derivatives exhibited better NO inhibitory activity than hydrocortisone sodium succinate, a glucocorticoid drug. The structure–activity relationship analysis indicated that the kinds of amino acid residues and their hydrophilicity influenced the activity to a great extent, as did <i>R</i>/<i>S</i> stereochemistry at C-24. Of the various derivatives, <b>5c</b> with an <i>N</i>-Boc-protected phenylalanine residue showed the highest NO inhibitory activity and relatively low cytotoxicity. Moreover, derivative <b>5c</b> could dose-dependently suppress iNOS, IL-1β, and TNF-α via the MAPK and NF-κB pathways, but not the GR pathway. Overall, pyxinol derivatives hold potential for application as anti-inflammatory agents.https://www.mdpi.com/1420-3049/28/3/1307pyxinolanti-inflammatory activityginsenosidesstructure–activity relationship |
| spellingShingle | Yunxiao Wang Xiaoliang Mi Yuan Du Shuang Li Liping Yu Meng Gao Xiaoyue Yang Zhihua Song Hui Yu Gangqiang Yang Design, Synthesis, and Anti-Inflammatory Activities of 12-Dehydropyxinol Derivatives Molecules pyxinol anti-inflammatory activity ginsenosides structure–activity relationship |
| title | Design, Synthesis, and Anti-Inflammatory Activities of 12-Dehydropyxinol Derivatives |
| title_full | Design, Synthesis, and Anti-Inflammatory Activities of 12-Dehydropyxinol Derivatives |
| title_fullStr | Design, Synthesis, and Anti-Inflammatory Activities of 12-Dehydropyxinol Derivatives |
| title_full_unstemmed | Design, Synthesis, and Anti-Inflammatory Activities of 12-Dehydropyxinol Derivatives |
| title_short | Design, Synthesis, and Anti-Inflammatory Activities of 12-Dehydropyxinol Derivatives |
| title_sort | design synthesis and anti inflammatory activities of 12 dehydropyxinol derivatives |
| topic | pyxinol anti-inflammatory activity ginsenosides structure–activity relationship |
| url | https://www.mdpi.com/1420-3049/28/3/1307 |
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