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Synthesis and Biological Evaluation of Novel Allobetulon/Allobetulin–Nucleoside Conjugates as AntitumorAgents
Allobetulin is structurally similar tobetulinic acid, inducing the apoptosis of cancer cells with low toxicity. However, both of them exhibited weak antiproliferation against several tumor cell lines. Therefore, the new series of allobetulon/allobetulin–nucleoside conjugates 9a–10i were designed and...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9329720/ https://www.ncbi.nlm.nih.gov/pubmed/35897914 http://dx.doi.org/10.3390/molecules27154738 |
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author | Wang, Yanli Huang, Xiaowan Zhang, Xiao Wang, Jingchen Li, Keyan Liu, Guotao Lu, Kexin Zhang, Xiang Xie, Chengping Zheng, Teresa Cheng, Yung-Yi Wang, Qiang |
author_facet | Wang, Yanli Huang, Xiaowan Zhang, Xiao Wang, Jingchen Li, Keyan Liu, Guotao Lu, Kexin Zhang, Xiang Xie, Chengping Zheng, Teresa Cheng, Yung-Yi Wang, Qiang |
author_sort | Wang, Yanli |
collection | PubMed |
description | Allobetulin is structurally similar tobetulinic acid, inducing the apoptosis of cancer cells with low toxicity. However, both of them exhibited weak antiproliferation against several tumor cell lines. Therefore, the new series of allobetulon/allobetulin–nucleoside conjugates 9a–10i were designed and synthesized for potency improvement. Compounds 9b, 9e, 10a, and 10d showed promising antiproliferative activity toward six tested cell lines, compared to zidovudine, cisplatin, and oxaliplatin based on their antitumor activity results. Among them, compound 10d exhibited much more potent antiproliferative activity against SMMC-7721, HepG2, MNK-45, SW620, and A549 human cancer cell lines than cisplatin and oxaliplatin. In the preliminary study for the mechanism of action, compound 10d induced cell apoptosis and autophagy in SMMC cells, resulting in antiproliferation and G0/G1 cell cycle arrest by regulating protein expression levels of Bax, Bcl-2, and LC3. Consequently, the nucleoside-conjugated allobetulin (10d) evidenced that nucleoside substitution was a viable strategy to improve allobetulin/allobetulon’s antitumor activity based on our present study. |
format | Online Article Text |
id | pubmed-9329720 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-93297202022-07-29 Synthesis and Biological Evaluation of Novel Allobetulon/Allobetulin–Nucleoside Conjugates as AntitumorAgents Wang, Yanli Huang, Xiaowan Zhang, Xiao Wang, Jingchen Li, Keyan Liu, Guotao Lu, Kexin Zhang, Xiang Xie, Chengping Zheng, Teresa Cheng, Yung-Yi Wang, Qiang Molecules Article Allobetulin is structurally similar tobetulinic acid, inducing the apoptosis of cancer cells with low toxicity. However, both of them exhibited weak antiproliferation against several tumor cell lines. Therefore, the new series of allobetulon/allobetulin–nucleoside conjugates 9a–10i were designed and synthesized for potency improvement. Compounds 9b, 9e, 10a, and 10d showed promising antiproliferative activity toward six tested cell lines, compared to zidovudine, cisplatin, and oxaliplatin based on their antitumor activity results. Among them, compound 10d exhibited much more potent antiproliferative activity against SMMC-7721, HepG2, MNK-45, SW620, and A549 human cancer cell lines than cisplatin and oxaliplatin. In the preliminary study for the mechanism of action, compound 10d induced cell apoptosis and autophagy in SMMC cells, resulting in antiproliferation and G0/G1 cell cycle arrest by regulating protein expression levels of Bax, Bcl-2, and LC3. Consequently, the nucleoside-conjugated allobetulin (10d) evidenced that nucleoside substitution was a viable strategy to improve allobetulin/allobetulon’s antitumor activity based on our present study. MDPI 2022-07-25 /pmc/articles/PMC9329720/ /pubmed/35897914 http://dx.doi.org/10.3390/molecules27154738 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Wang, Yanli Huang, Xiaowan Zhang, Xiao Wang, Jingchen Li, Keyan Liu, Guotao Lu, Kexin Zhang, Xiang Xie, Chengping Zheng, Teresa Cheng, Yung-Yi Wang, Qiang Synthesis and Biological Evaluation of Novel Allobetulon/Allobetulin–Nucleoside Conjugates as AntitumorAgents |
title | Synthesis and Biological Evaluation of Novel Allobetulon/Allobetulin–Nucleoside Conjugates as AntitumorAgents |
title_full | Synthesis and Biological Evaluation of Novel Allobetulon/Allobetulin–Nucleoside Conjugates as AntitumorAgents |
title_fullStr | Synthesis and Biological Evaluation of Novel Allobetulon/Allobetulin–Nucleoside Conjugates as AntitumorAgents |
title_full_unstemmed | Synthesis and Biological Evaluation of Novel Allobetulon/Allobetulin–Nucleoside Conjugates as AntitumorAgents |
title_short | Synthesis and Biological Evaluation of Novel Allobetulon/Allobetulin–Nucleoside Conjugates as AntitumorAgents |
title_sort | synthesis and biological evaluation of novel allobetulon/allobetulin–nucleoside conjugates as antitumoragents |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9329720/ https://www.ncbi.nlm.nih.gov/pubmed/35897914 http://dx.doi.org/10.3390/molecules27154738 |
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