Native Endophytes of Tripterygium wilfordii-Mediated Biotransformation Reduces Toxicity of Celastrol
Celastrol (1), obtained from the roots of Tripterygium wilfordii Hook F., is most likely to become an antitumor drug, but with severe cytotoxicity. Due to the lack of modifiable sites in the structure of celastrol, the structural diversity of the modified products obtained by synthesis in the previo...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-05-01
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| Series: | Frontiers in Microbiology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fmicb.2022.810565/full |
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| author | Ping-yang Ma Wei-ling Geng Hong-yan Ji Bang-wen Yue Cheng Liu Sa Wang Zhi-bo Jiang Jing Chen Xiu-li Wu |
| author_facet | Ping-yang Ma Wei-ling Geng Hong-yan Ji Bang-wen Yue Cheng Liu Sa Wang Zhi-bo Jiang Jing Chen Xiu-li Wu |
| author_sort | Ping-yang Ma |
| collection | DOAJ |
| description | Celastrol (1), obtained from the roots of Tripterygium wilfordii Hook F., is most likely to become an antitumor drug, but with severe cytotoxicity. Due to the lack of modifiable sites in the structure of celastrol, the structural diversity of the modified products obtained by synthesis in the previous studies is insufficient, which hinders the pace of its patent medicine. This study describes a method of microbial transformation to increase the modification site of celastrol and reduce its toxicity. The screening of endophytes from native plants was introduced in this context, which led to two novel stereoselective oxidation products such as S-16-hydroxyl celastrol (2) and A-ring aromatized S-16-hydroxyl celastrol (3), along with a rare 7,9-octadecadienoic acid ester of celastrol (4). Their structures were determined by extensive spectroscopic data analysis, especially 1D and 2D NMR. Compared with 1, compounds 3 and 4 exhibited similar antitumor activity in U251, A549, KG-1, and B16 cell lines. Compound 2 had slightly decreased antitumor activity when compared with compound 1. Furthermore, compound 2–4 showed lower cytotoxicity against BV-2 (about 21-fold lower, 2: 92.82 μM, 3: 34.25 μM, and 4: 74.75 μM vs. celastrol: 4.35 μM), and also identical trends against H9c2 and PC12 cell lines. |
| first_indexed | 2024-04-14T00:14:23Z |
| format | Article |
| id | doaj.art-988db4dd09c248098036f15b56fd6f6a |
| institution | Directory Open Access Journal |
| issn | 1664-302X |
| language | English |
| last_indexed | 2024-04-14T00:14:23Z |
| publishDate | 2022-05-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Microbiology |
| spelling | doaj.art-988db4dd09c248098036f15b56fd6f6a2022-12-22T02:23:12ZengFrontiers Media S.A.Frontiers in Microbiology1664-302X2022-05-011310.3389/fmicb.2022.810565810565Native Endophytes of Tripterygium wilfordii-Mediated Biotransformation Reduces Toxicity of CelastrolPing-yang Ma0Wei-ling Geng1Hong-yan Ji2Bang-wen Yue3Cheng Liu4Sa Wang5Zhi-bo Jiang6Jing Chen7Xiu-li Wu8College of Pharmacy, Ningxia Medical University, Yinchuan, ChinaCollege of Pharmacy, Ningxia Medical University, Yinchuan, ChinaDepartment of Pharmaceutics, General Hospital of Ningxia Medical University, Yinchuan, ChinaCollege of Pharmacy, Ningxia Medical University, Yinchuan, ChinaCollege of Pharmacy, Ningxia Medical University, Yinchuan, ChinaCollege of Pharmacy, Ningxia Medical University, Yinchuan, ChinaKey Laboratory for Chemical Engineering and Technology, School of Chemistry and Chemical Engineering, State Ethnic Affairs Commission, North Minzu University, Yinchuan, ChinaInstitute of Translational Medicine, Medical College, Yangzhou University, Yangzhou, ChinaCollege of Pharmacy, Ningxia Medical University, Yinchuan, ChinaCelastrol (1), obtained from the roots of Tripterygium wilfordii Hook F., is most likely to become an antitumor drug, but with severe cytotoxicity. Due to the lack of modifiable sites in the structure of celastrol, the structural diversity of the modified products obtained by synthesis in the previous studies is insufficient, which hinders the pace of its patent medicine. This study describes a method of microbial transformation to increase the modification site of celastrol and reduce its toxicity. The screening of endophytes from native plants was introduced in this context, which led to two novel stereoselective oxidation products such as S-16-hydroxyl celastrol (2) and A-ring aromatized S-16-hydroxyl celastrol (3), along with a rare 7,9-octadecadienoic acid ester of celastrol (4). Their structures were determined by extensive spectroscopic data analysis, especially 1D and 2D NMR. Compared with 1, compounds 3 and 4 exhibited similar antitumor activity in U251, A549, KG-1, and B16 cell lines. Compound 2 had slightly decreased antitumor activity when compared with compound 1. Furthermore, compound 2–4 showed lower cytotoxicity against BV-2 (about 21-fold lower, 2: 92.82 μM, 3: 34.25 μM, and 4: 74.75 μM vs. celastrol: 4.35 μM), and also identical trends against H9c2 and PC12 cell lines.https://www.frontiersin.org/articles/10.3389/fmicb.2022.810565/fullcelastrolbio-transformationendophytereduce toxicityhydroxylation |
| spellingShingle | Ping-yang Ma Wei-ling Geng Hong-yan Ji Bang-wen Yue Cheng Liu Sa Wang Zhi-bo Jiang Jing Chen Xiu-li Wu Native Endophytes of Tripterygium wilfordii-Mediated Biotransformation Reduces Toxicity of Celastrol Frontiers in Microbiology celastrol bio-transformation endophyte reduce toxicity hydroxylation |
| title | Native Endophytes of Tripterygium wilfordii-Mediated Biotransformation Reduces Toxicity of Celastrol |
| title_full | Native Endophytes of Tripterygium wilfordii-Mediated Biotransformation Reduces Toxicity of Celastrol |
| title_fullStr | Native Endophytes of Tripterygium wilfordii-Mediated Biotransformation Reduces Toxicity of Celastrol |
| title_full_unstemmed | Native Endophytes of Tripterygium wilfordii-Mediated Biotransformation Reduces Toxicity of Celastrol |
| title_short | Native Endophytes of Tripterygium wilfordii-Mediated Biotransformation Reduces Toxicity of Celastrol |
| title_sort | native endophytes of tripterygium wilfordii mediated biotransformation reduces toxicity of celastrol |
| topic | celastrol bio-transformation endophyte reduce toxicity hydroxylation |
| url | https://www.frontiersin.org/articles/10.3389/fmicb.2022.810565/full |
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