Design, Synthesis, and Biological Evaluation of Novel Nitrogen Heterocycle-Containing Ursolic Acid Analogs as Antitumor Agents

Nineteen ursolic acid analogues were designed, synthesized, and evaluated for their antiproliferative activity against the Hela and MKN45 cell lines. Some compounds containing a piperazine moiety displayed moderate to high levels of antitumor activities against the tested cancer cell lines. The most...

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Detalles Bibliográficos
Autores principales: Wang, Wenzhi, Lei, Lei, Liu, Zhi, Wang, Hongbo, Meng, Qingguo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6429512/
https://www.ncbi.nlm.nih.gov/pubmed/30832266
http://dx.doi.org/10.3390/molecules24050877
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author Wang, Wenzhi
Lei, Lei
Liu, Zhi
Wang, Hongbo
Meng, Qingguo
author_facet Wang, Wenzhi
Lei, Lei
Liu, Zhi
Wang, Hongbo
Meng, Qingguo
author_sort Wang, Wenzhi
collection PubMed
description Nineteen ursolic acid analogues were designed, synthesized, and evaluated for their antiproliferative activity against the Hela and MKN45 cell lines. Some compounds containing a piperazine moiety displayed moderate to high levels of antitumor activities against the tested cancer cell lines. The most potent compound shares the IC(50) value of 2.1 µM and 2.6 µM for the Hela and MKN45 cell lines, respectively. Further mechanism studies and in vivo antitumor studies have shown that it decreased the apoptosis regulator (BCL2/BAX) ratio, disrupted mitochondrial potential and induced apoptosis, and suppressed the growth of Hela xenografts in nude mice.
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spelling pubmed-64295122019-04-15 Design, Synthesis, and Biological Evaluation of Novel Nitrogen Heterocycle-Containing Ursolic Acid Analogs as Antitumor Agents Wang, Wenzhi Lei, Lei Liu, Zhi Wang, Hongbo Meng, Qingguo Molecules Article Nineteen ursolic acid analogues were designed, synthesized, and evaluated for their antiproliferative activity against the Hela and MKN45 cell lines. Some compounds containing a piperazine moiety displayed moderate to high levels of antitumor activities against the tested cancer cell lines. The most potent compound shares the IC(50) value of 2.1 µM and 2.6 µM for the Hela and MKN45 cell lines, respectively. Further mechanism studies and in vivo antitumor studies have shown that it decreased the apoptosis regulator (BCL2/BAX) ratio, disrupted mitochondrial potential and induced apoptosis, and suppressed the growth of Hela xenografts in nude mice. MDPI 2019-03-01 /pmc/articles/PMC6429512/ /pubmed/30832266 http://dx.doi.org/10.3390/molecules24050877 Text en © 2019 by the authors. 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 (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Wang, Wenzhi
Lei, Lei
Liu, Zhi
Wang, Hongbo
Meng, Qingguo
Design, Synthesis, and Biological Evaluation of Novel Nitrogen Heterocycle-Containing Ursolic Acid Analogs as Antitumor Agents
title Design, Synthesis, and Biological Evaluation of Novel Nitrogen Heterocycle-Containing Ursolic Acid Analogs as Antitumor Agents
title_full Design, Synthesis, and Biological Evaluation of Novel Nitrogen Heterocycle-Containing Ursolic Acid Analogs as Antitumor Agents
title_fullStr Design, Synthesis, and Biological Evaluation of Novel Nitrogen Heterocycle-Containing Ursolic Acid Analogs as Antitumor Agents
title_full_unstemmed Design, Synthesis, and Biological Evaluation of Novel Nitrogen Heterocycle-Containing Ursolic Acid Analogs as Antitumor Agents
title_short Design, Synthesis, and Biological Evaluation of Novel Nitrogen Heterocycle-Containing Ursolic Acid Analogs as Antitumor Agents
title_sort design, synthesis, and biological evaluation of novel nitrogen heterocycle-containing ursolic acid analogs as antitumor agents
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6429512/
https://www.ncbi.nlm.nih.gov/pubmed/30832266
http://dx.doi.org/10.3390/molecules24050877
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AT wanghongbo designsynthesisandbiologicalevaluationofnovelnitrogenheterocyclecontainingursolicacidanalogsasantitumoragents
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