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Design, synthesis and cytotoxic evaluation of novel betulonic acid-diazine derivatives as potential antitumor agents

With the purpose to improve antiproliferative activity, 26 new betulonic acid-diazine derivatives were designed and synthesized from betulinic acid. The anticancer activity of these semi-synthetic compounds was evaluated by MTT assay in both tumor cell lines and normal cell line. The results indicat...

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Autores principales: Shu, Yisong, Li, Feifei, Han, Yaotian, Wang, Penglong, Gao, Feng, Yan, Mengmeng, Liang, Miao, Ma, Qiang, Zhang, Yuzhong, Ding, Xia, Lei, Haimin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9486541/
https://www.ncbi.nlm.nih.gov/pubmed/36147251
http://dx.doi.org/10.3389/fchem.2022.969770
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author Shu, Yisong
Li, Feifei
Han, Yaotian
Wang, Penglong
Gao, Feng
Yan, Mengmeng
Liang, Miao
Ma, Qiang
Zhang, Yuzhong
Ding, Xia
Lei, Haimin
author_facet Shu, Yisong
Li, Feifei
Han, Yaotian
Wang, Penglong
Gao, Feng
Yan, Mengmeng
Liang, Miao
Ma, Qiang
Zhang, Yuzhong
Ding, Xia
Lei, Haimin
author_sort Shu, Yisong
collection PubMed
description With the purpose to improve antiproliferative activity, 26 new betulonic acid-diazine derivatives were designed and synthesized from betulinic acid. The anticancer activity of these semi-synthetic compounds was evaluated by MTT assay in both tumor cell lines and normal cell line. The results indicated that majority of new compounds exhibited improved antitumor activity compared with the parent compound betulonic acid. Compound BoA2C, in particular, had the most significant action with IC(50) value of 3.39 μM against MCF-7 cells, while it showed lower cytotoxicity on MDCK cell line than cisplatin. Furthermore, we discovered that BoA2C strongly increased MCF-7 cell damage mostly by influencing arginine and fatty acid metabolism. In addition, the structure-activity relationships were briefly discussed. The results of this study suggested that the introduction of different diazines at C-28 could selectively inhibit different kinds of cancer cells and might be an effective way to synthesize potent anticancer lead compound from betulonic acid.
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spelling pubmed-94865412022-09-21 Design, synthesis and cytotoxic evaluation of novel betulonic acid-diazine derivatives as potential antitumor agents Shu, Yisong Li, Feifei Han, Yaotian Wang, Penglong Gao, Feng Yan, Mengmeng Liang, Miao Ma, Qiang Zhang, Yuzhong Ding, Xia Lei, Haimin Front Chem Chemistry With the purpose to improve antiproliferative activity, 26 new betulonic acid-diazine derivatives were designed and synthesized from betulinic acid. The anticancer activity of these semi-synthetic compounds was evaluated by MTT assay in both tumor cell lines and normal cell line. The results indicated that majority of new compounds exhibited improved antitumor activity compared with the parent compound betulonic acid. Compound BoA2C, in particular, had the most significant action with IC(50) value of 3.39 μM against MCF-7 cells, while it showed lower cytotoxicity on MDCK cell line than cisplatin. Furthermore, we discovered that BoA2C strongly increased MCF-7 cell damage mostly by influencing arginine and fatty acid metabolism. In addition, the structure-activity relationships were briefly discussed. The results of this study suggested that the introduction of different diazines at C-28 could selectively inhibit different kinds of cancer cells and might be an effective way to synthesize potent anticancer lead compound from betulonic acid. Frontiers Media S.A. 2022-09-06 /pmc/articles/PMC9486541/ /pubmed/36147251 http://dx.doi.org/10.3389/fchem.2022.969770 Text en Copyright © 2022 Shu, Li, Han, Wang, Gao, Yan, Liang, Ma, Zhang, Ding and Lei. 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 Chemistry
Shu, Yisong
Li, Feifei
Han, Yaotian
Wang, Penglong
Gao, Feng
Yan, Mengmeng
Liang, Miao
Ma, Qiang
Zhang, Yuzhong
Ding, Xia
Lei, Haimin
Design, synthesis and cytotoxic evaluation of novel betulonic acid-diazine derivatives as potential antitumor agents
title Design, synthesis and cytotoxic evaluation of novel betulonic acid-diazine derivatives as potential antitumor agents
title_full Design, synthesis and cytotoxic evaluation of novel betulonic acid-diazine derivatives as potential antitumor agents
title_fullStr Design, synthesis and cytotoxic evaluation of novel betulonic acid-diazine derivatives as potential antitumor agents
title_full_unstemmed Design, synthesis and cytotoxic evaluation of novel betulonic acid-diazine derivatives as potential antitumor agents
title_short Design, synthesis and cytotoxic evaluation of novel betulonic acid-diazine derivatives as potential antitumor agents
title_sort design, synthesis and cytotoxic evaluation of novel betulonic acid-diazine derivatives as potential antitumor agents
topic Chemistry
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9486541/
https://www.ncbi.nlm.nih.gov/pubmed/36147251
http://dx.doi.org/10.3389/fchem.2022.969770
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