BCESA: a nano-scaled intercalator capable of targeting tumor tissue and releasing anti-tumoral β-carboline-3-carboxylic acid

Jianhui Wu,1,2 Yue Cui,1,2 Xiaoyi Zhang,1,2 Lin Gui,1,2 Yaonan Wang,1,2 Shiqi Peng,1,2 Ming Zhao1–31Beijing Area Major Laboratory of Peptide and Small Molecular Drugs, School of Pharmaceutical Sciences, Capital Medical University, Beijing 100069, People’s Republic of China; 2Engi...

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Autores principales: Wu J, Cui Y, Zhang X, Gui L, Wang Y, Peng S, Zhao M
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Publicado: Dove Medical Press 2019
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spelling oai:doaj.org-article:fb4a633b6518483fa154b0f2d320b0f32021-12-02T03:57:25ZBCESA: a nano-scaled intercalator capable of targeting tumor tissue and releasing anti-tumoral β-carboline-3-carboxylic acid1178-2013https://doaj.org/article/fb4a633b6518483fa154b0f2d320b0f32019-04-01T00:00:00Zhttps://www.dovepress.com/bcesa-a-nano-scaled-intercalator-capable-of-targeting-tumor-tissue-and-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Jianhui Wu,1,2 Yue Cui,1,2 Xiaoyi Zhang,1,2 Lin Gui,1,2 Yaonan Wang,1,2 Shiqi Peng,1,2 Ming Zhao1–31Beijing Area Major Laboratory of Peptide and Small Molecular Drugs, School of Pharmaceutical Sciences, Capital Medical University, Beijing 100069, People’s Republic of China; 2Engineering Research Center of Endogenous Prophylactic of Ministry of Education of China, School of Pharmaceutical Sciences, Capital Medical University, Beijing 100069, People’s Republic of China; 3Beijing Laboratory of Biomedical Materials and Key Laboratory of Biomedical Materials of Natural Macromolecules (Beijing University of Chemical Technology), Ministry of Education, Beijing, People’s Republic of ChinaBackground: In the discovery of DNA intercalators, β-carbolines compose one member of the most interesting alkaloid family and are of clinical importance. In the efforts, N-(3-benzyloxycarbonyl-β-carboline-1-yl)ethyl-Ser-Ala-OBzl (BCESA) was designed as a nano-scaled DNA intercalator without Dox-like toxicity.Methods: Based on the structural analysis and CDOCKER energy comparison, BCESA was rationally designed as such a nano-scaled intercalator. The anti-tumor activity, the toxicity and the tumor targeting action of BCESA were evaluated on mouse models.Results: The in vitro proliferation of cancer cells, but not non-cancer cells, was effectively inhibited by BCESA. On S180 mouse model BCESA dose-dependently slowed the tumor growth, and 0.01 μmol/kg/day was found as a minimal effective dose. Both BCESA and its moiety were found in the tumor tissue, but not in the organs and the blood, of S180 mice.Conclusion: BCESA should be a nano-scaled intercalator capable of targeting tumor tissue to release anti-tumoral β-carboline-3-carboxylic acid and its 1-methyl derivative, while Ser-Ala-OBzl is a simple and desirable carrier.Keywords: nano-medicine, β-carboline, intercalator, d(AGACGTCT)2, anti-tumorWu JCui YZhang XGui LWang YPeng SZhao MDove Medical PressarticleKeywords nano-medicineβ-carbolineintercalatord(AGACGTCT)2anti-tumorMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 14, Pp 3027-3041 (2019)
institution DOAJ
collection DOAJ
language EN
topic Keywords nano-medicine
β-carboline
intercalator
d(AGACGTCT)2
anti-tumor
Medicine (General)
R5-920
spellingShingle Keywords nano-medicine
β-carboline
intercalator
d(AGACGTCT)2
anti-tumor
Medicine (General)
R5-920
Wu J
Cui Y
Zhang X
Gui L
Wang Y
Peng S
Zhao M
BCESA: a nano-scaled intercalator capable of targeting tumor tissue and releasing anti-tumoral β-carboline-3-carboxylic acid
description Jianhui Wu,1,2 Yue Cui,1,2 Xiaoyi Zhang,1,2 Lin Gui,1,2 Yaonan Wang,1,2 Shiqi Peng,1,2 Ming Zhao1–31Beijing Area Major Laboratory of Peptide and Small Molecular Drugs, School of Pharmaceutical Sciences, Capital Medical University, Beijing 100069, People’s Republic of China; 2Engineering Research Center of Endogenous Prophylactic of Ministry of Education of China, School of Pharmaceutical Sciences, Capital Medical University, Beijing 100069, People’s Republic of China; 3Beijing Laboratory of Biomedical Materials and Key Laboratory of Biomedical Materials of Natural Macromolecules (Beijing University of Chemical Technology), Ministry of Education, Beijing, People’s Republic of ChinaBackground: In the discovery of DNA intercalators, β-carbolines compose one member of the most interesting alkaloid family and are of clinical importance. In the efforts, N-(3-benzyloxycarbonyl-β-carboline-1-yl)ethyl-Ser-Ala-OBzl (BCESA) was designed as a nano-scaled DNA intercalator without Dox-like toxicity.Methods: Based on the structural analysis and CDOCKER energy comparison, BCESA was rationally designed as such a nano-scaled intercalator. The anti-tumor activity, the toxicity and the tumor targeting action of BCESA were evaluated on mouse models.Results: The in vitro proliferation of cancer cells, but not non-cancer cells, was effectively inhibited by BCESA. On S180 mouse model BCESA dose-dependently slowed the tumor growth, and 0.01 μmol/kg/day was found as a minimal effective dose. Both BCESA and its moiety were found in the tumor tissue, but not in the organs and the blood, of S180 mice.Conclusion: BCESA should be a nano-scaled intercalator capable of targeting tumor tissue to release anti-tumoral β-carboline-3-carboxylic acid and its 1-methyl derivative, while Ser-Ala-OBzl is a simple and desirable carrier.Keywords: nano-medicine, β-carboline, intercalator, d(AGACGTCT)2, anti-tumor
format article
author Wu J
Cui Y
Zhang X
Gui L
Wang Y
Peng S
Zhao M
author_facet Wu J
Cui Y
Zhang X
Gui L
Wang Y
Peng S
Zhao M
author_sort Wu J
title BCESA: a nano-scaled intercalator capable of targeting tumor tissue and releasing anti-tumoral β-carboline-3-carboxylic acid
title_short BCESA: a nano-scaled intercalator capable of targeting tumor tissue and releasing anti-tumoral β-carboline-3-carboxylic acid
title_full BCESA: a nano-scaled intercalator capable of targeting tumor tissue and releasing anti-tumoral β-carboline-3-carboxylic acid
title_fullStr BCESA: a nano-scaled intercalator capable of targeting tumor tissue and releasing anti-tumoral β-carboline-3-carboxylic acid
title_full_unstemmed BCESA: a nano-scaled intercalator capable of targeting tumor tissue and releasing anti-tumoral β-carboline-3-carboxylic acid
title_sort bcesa: a nano-scaled intercalator capable of targeting tumor tissue and releasing anti-tumoral β-carboline-3-carboxylic acid
publisher Dove Medical Press
publishDate 2019
url https://doaj.org/article/fb4a633b6518483fa154b0f2d320b0f3
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