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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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Autores principales: Ma, Ping-yang, Geng, Wei-ling, Ji, Hong-yan, Yue, Bang-wen, Liu, Cheng, Wang, Sa, Jiang, Zhi-bo, Chen, Jing, Wu, Xiu-li
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9177160/
https://www.ncbi.nlm.nih.gov/pubmed/35694316
http://dx.doi.org/10.3389/fmicb.2022.810565
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author Ma, Ping-yang
Geng, Wei-ling
Ji, Hong-yan
Yue, Bang-wen
Liu, Cheng
Wang, Sa
Jiang, Zhi-bo
Chen, Jing
Wu, Xiu-li
author_facet Ma, Ping-yang
Geng, Wei-ling
Ji, Hong-yan
Yue, Bang-wen
Liu, Cheng
Wang, Sa
Jiang, Zhi-bo
Chen, Jing
Wu, Xiu-li
author_sort Ma, Ping-yang
collection PubMed
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.
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spelling pubmed-91771602022-06-09 Native Endophytes of Tripterygium wilfordii-Mediated Biotransformation Reduces Toxicity of Celastrol Ma, Ping-yang Geng, Wei-ling Ji, Hong-yan Yue, Bang-wen Liu, Cheng Wang, Sa Jiang, Zhi-bo Chen, Jing Wu, Xiu-li Front Microbiol Microbiology 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. Frontiers Media S.A. 2022-05-25 /pmc/articles/PMC9177160/ /pubmed/35694316 http://dx.doi.org/10.3389/fmicb.2022.810565 Text en Copyright © 2022 Ma, Geng, Ji, Yue, Liu, Wang, Jiang, Chen and Wu. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Microbiology
Ma, Ping-yang
Geng, Wei-ling
Ji, Hong-yan
Yue, Bang-wen
Liu, Cheng
Wang, Sa
Jiang, Zhi-bo
Chen, Jing
Wu, Xiu-li
Native Endophytes of Tripterygium wilfordii-Mediated Biotransformation Reduces Toxicity of Celastrol
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 Microbiology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9177160/
https://www.ncbi.nlm.nih.gov/pubmed/35694316
http://dx.doi.org/10.3389/fmicb.2022.810565
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