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Preparation of 6/8/11-Amino/Chloro-Oxoisoaporphine and Group-10 Metal Complexes and Evaluation of Their in Vitro and in Vivo Antitumor Activity

A series of group-10 metal complexes 1–14 of oxoisoaporphine derivatives were designed and synthesized. 1–14 were more selectively cytotoxic to Hep-G2 cells comparing with normal liver cells. In vitro cytotoxicity results showed that complexes 1–6, 7, 8, 10 and 11, especially 3, were telomerase inhi...

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Autores principales: Qin, Qi-Pin, Qin, Jiao-Lan, Meng, Ting, Yang, Gui-Ai, Wei, Zu-Zhuang, Liu, Yan-Cheng, Liang, Hong, Chen, Zhen-Feng
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5127189/
https://www.ncbi.nlm.nih.gov/pubmed/27898051
http://dx.doi.org/10.1038/srep37644
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author Qin, Qi-Pin
Qin, Jiao-Lan
Meng, Ting
Yang, Gui-Ai
Wei, Zu-Zhuang
Liu, Yan-Cheng
Liang, Hong
Chen, Zhen-Feng
author_facet Qin, Qi-Pin
Qin, Jiao-Lan
Meng, Ting
Yang, Gui-Ai
Wei, Zu-Zhuang
Liu, Yan-Cheng
Liang, Hong
Chen, Zhen-Feng
author_sort Qin, Qi-Pin
collection PubMed
description A series of group-10 metal complexes 1–14 of oxoisoaporphine derivatives were designed and synthesized. 1–14 were more selectively cytotoxic to Hep-G2 cells comparing with normal liver cells. In vitro cytotoxicity results showed that complexes 1–6, 7, 8, 10 and 11, especially 3, were telomerase inhibitors targeting c-myc, telomeric, and bcl-2 G4s and triggered cell senescence and apoptosis; they also caused telomere/DNA damage and S phase arrest. In addition, 1–6 also caused mitochondrial dysfunction. Notably, 3 with 6-amino substituted ligand L(a) exhibited less side effects than 6 with 8-amino substituted ligand L(b) and cisplatin, but similar tumor growth inhibition efficacy in BEL-7402 xenograft model. Complex 3 has the potential to be developed as an effective anticancer agent.
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spelling pubmed-51271892016-12-09 Preparation of 6/8/11-Amino/Chloro-Oxoisoaporphine and Group-10 Metal Complexes and Evaluation of Their in Vitro and in Vivo Antitumor Activity Qin, Qi-Pin Qin, Jiao-Lan Meng, Ting Yang, Gui-Ai Wei, Zu-Zhuang Liu, Yan-Cheng Liang, Hong Chen, Zhen-Feng Sci Rep Article A series of group-10 metal complexes 1–14 of oxoisoaporphine derivatives were designed and synthesized. 1–14 were more selectively cytotoxic to Hep-G2 cells comparing with normal liver cells. In vitro cytotoxicity results showed that complexes 1–6, 7, 8, 10 and 11, especially 3, were telomerase inhibitors targeting c-myc, telomeric, and bcl-2 G4s and triggered cell senescence and apoptosis; they also caused telomere/DNA damage and S phase arrest. In addition, 1–6 also caused mitochondrial dysfunction. Notably, 3 with 6-amino substituted ligand L(a) exhibited less side effects than 6 with 8-amino substituted ligand L(b) and cisplatin, but similar tumor growth inhibition efficacy in BEL-7402 xenograft model. Complex 3 has the potential to be developed as an effective anticancer agent. Nature Publishing Group 2016-11-29 /pmc/articles/PMC5127189/ /pubmed/27898051 http://dx.doi.org/10.1038/srep37644 Text en Copyright © 2016, The Author(s) http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
spellingShingle Article
Qin, Qi-Pin
Qin, Jiao-Lan
Meng, Ting
Yang, Gui-Ai
Wei, Zu-Zhuang
Liu, Yan-Cheng
Liang, Hong
Chen, Zhen-Feng
Preparation of 6/8/11-Amino/Chloro-Oxoisoaporphine and Group-10 Metal Complexes and Evaluation of Their in Vitro and in Vivo Antitumor Activity
title Preparation of 6/8/11-Amino/Chloro-Oxoisoaporphine and Group-10 Metal Complexes and Evaluation of Their in Vitro and in Vivo Antitumor Activity
title_full Preparation of 6/8/11-Amino/Chloro-Oxoisoaporphine and Group-10 Metal Complexes and Evaluation of Their in Vitro and in Vivo Antitumor Activity
title_fullStr Preparation of 6/8/11-Amino/Chloro-Oxoisoaporphine and Group-10 Metal Complexes and Evaluation of Their in Vitro and in Vivo Antitumor Activity
title_full_unstemmed Preparation of 6/8/11-Amino/Chloro-Oxoisoaporphine and Group-10 Metal Complexes and Evaluation of Their in Vitro and in Vivo Antitumor Activity
title_short Preparation of 6/8/11-Amino/Chloro-Oxoisoaporphine and Group-10 Metal Complexes and Evaluation of Their in Vitro and in Vivo Antitumor Activity
title_sort preparation of 6/8/11-amino/chloro-oxoisoaporphine and group-10 metal complexes and evaluation of their in vitro and in vivo antitumor activity
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5127189/
https://www.ncbi.nlm.nih.gov/pubmed/27898051
http://dx.doi.org/10.1038/srep37644
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