Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
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
_version_ 1784757982890819584
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
work_keys_str_mv AT wangyanli synthesisandbiologicalevaluationofnovelallobetulonallobetulinnucleosideconjugatesasantitumoragents
AT huangxiaowan synthesisandbiologicalevaluationofnovelallobetulonallobetulinnucleosideconjugatesasantitumoragents
AT zhangxiao synthesisandbiologicalevaluationofnovelallobetulonallobetulinnucleosideconjugatesasantitumoragents
AT wangjingchen synthesisandbiologicalevaluationofnovelallobetulonallobetulinnucleosideconjugatesasantitumoragents
AT likeyan synthesisandbiologicalevaluationofnovelallobetulonallobetulinnucleosideconjugatesasantitumoragents
AT liuguotao synthesisandbiologicalevaluationofnovelallobetulonallobetulinnucleosideconjugatesasantitumoragents
AT lukexin synthesisandbiologicalevaluationofnovelallobetulonallobetulinnucleosideconjugatesasantitumoragents
AT zhangxiang synthesisandbiologicalevaluationofnovelallobetulonallobetulinnucleosideconjugatesasantitumoragents
AT xiechengping synthesisandbiologicalevaluationofnovelallobetulonallobetulinnucleosideconjugatesasantitumoragents
AT zhengteresa synthesisandbiologicalevaluationofnovelallobetulonallobetulinnucleosideconjugatesasantitumoragents
AT chengyungyi synthesisandbiologicalevaluationofnovelallobetulonallobetulinnucleosideconjugatesasantitumoragents
AT wangqiang synthesisandbiologicalevaluationofnovelallobetulonallobetulinnucleosideconjugatesasantitumoragents