Cargando…

Synthesis and Biological Activities of a 3′-Azido Analogue of Doxorubicin Against Drug-Resistant Cancer Cells

Doxorubicin (DOX), an anthracycline antibiotic, is one of the most active anticancer chemotherapeutic agents. The clinical use of DOX, however, is limited by the dose-dependant P-glycoprotein (P-gp)-mediated resistance. Herein, a 3′-azido analogue of DOX (ADOX) was prepared from daunorubicin (DNR)....

Descripción completa

Detalles Bibliográficos
Autores principales: Yu, Shuwen, Zhang, Guisheng, Zhang, Wenpeng, Luo, Huanhua, Qiu, Liyun, Liu, Qingfeng, Sun, Duxin, Wang, Peng-George, Wang, Fengshan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Molecular Diversity Preservation International (MDPI) 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3317735/
https://www.ncbi.nlm.nih.gov/pubmed/22489175
http://dx.doi.org/10.3390/ijms13033671
_version_ 1782228610842624000
author Yu, Shuwen
Zhang, Guisheng
Zhang, Wenpeng
Luo, Huanhua
Qiu, Liyun
Liu, Qingfeng
Sun, Duxin
Wang, Peng-George
Wang, Fengshan
author_facet Yu, Shuwen
Zhang, Guisheng
Zhang, Wenpeng
Luo, Huanhua
Qiu, Liyun
Liu, Qingfeng
Sun, Duxin
Wang, Peng-George
Wang, Fengshan
author_sort Yu, Shuwen
collection PubMed
description Doxorubicin (DOX), an anthracycline antibiotic, is one of the most active anticancer chemotherapeutic agents. The clinical use of DOX, however, is limited by the dose-dependant P-glycoprotein (P-gp)-mediated resistance. Herein, a 3′-azido analogue of DOX (ADOX) was prepared from daunorubicin (DNR). ADOX exhibited potent antitumor activities in drug-sensitive (MCF-7 and K562) and drug-resistant cell lines (MCF-7/DNR, K562/DOX), respectively. The drug resistance index (DRI) values of ADOX were much lower than that of DOX. The cytotoxicity experiments of ADOX or DOX against K562/DOX, with or without P-gp inhibitor, indicated that ADOX circumvents resistance by abolishing the P-gp recognition. This conclusion was further supported by drug influx/efflux flow cytometry experiments, as well as by molecular docking of ADOX to P-gp. In vivo animal tests, ADOX exhibited higher activity and less toxicity than DOX. The current data warranted ADOX for additional pre-clinical evaluations for new drug development.
format Online
Article
Text
id pubmed-3317735
institution National Center for Biotechnology Information
language English
publishDate 2012
publisher Molecular Diversity Preservation International (MDPI)
record_format MEDLINE/PubMed
spelling pubmed-33177352012-04-09 Synthesis and Biological Activities of a 3′-Azido Analogue of Doxorubicin Against Drug-Resistant Cancer Cells Yu, Shuwen Zhang, Guisheng Zhang, Wenpeng Luo, Huanhua Qiu, Liyun Liu, Qingfeng Sun, Duxin Wang, Peng-George Wang, Fengshan Int J Mol Sci Article Doxorubicin (DOX), an anthracycline antibiotic, is one of the most active anticancer chemotherapeutic agents. The clinical use of DOX, however, is limited by the dose-dependant P-glycoprotein (P-gp)-mediated resistance. Herein, a 3′-azido analogue of DOX (ADOX) was prepared from daunorubicin (DNR). ADOX exhibited potent antitumor activities in drug-sensitive (MCF-7 and K562) and drug-resistant cell lines (MCF-7/DNR, K562/DOX), respectively. The drug resistance index (DRI) values of ADOX were much lower than that of DOX. The cytotoxicity experiments of ADOX or DOX against K562/DOX, with or without P-gp inhibitor, indicated that ADOX circumvents resistance by abolishing the P-gp recognition. This conclusion was further supported by drug influx/efflux flow cytometry experiments, as well as by molecular docking of ADOX to P-gp. In vivo animal tests, ADOX exhibited higher activity and less toxicity than DOX. The current data warranted ADOX for additional pre-clinical evaluations for new drug development. Molecular Diversity Preservation International (MDPI) 2012-03-19 /pmc/articles/PMC3317735/ /pubmed/22489175 http://dx.doi.org/10.3390/ijms13033671 Text en © 2012 by the authors; licensee Molecular Diversity Preservation International, Basel, Switzerland. http://creativecommons.org/licenses/by/3.0 This article is an open-access article distributed under the terms and conditions of the Creative Commons Attribution license (http://creativecommons.org/licenses/by/3.0/).
spellingShingle Article
Yu, Shuwen
Zhang, Guisheng
Zhang, Wenpeng
Luo, Huanhua
Qiu, Liyun
Liu, Qingfeng
Sun, Duxin
Wang, Peng-George
Wang, Fengshan
Synthesis and Biological Activities of a 3′-Azido Analogue of Doxorubicin Against Drug-Resistant Cancer Cells
title Synthesis and Biological Activities of a 3′-Azido Analogue of Doxorubicin Against Drug-Resistant Cancer Cells
title_full Synthesis and Biological Activities of a 3′-Azido Analogue of Doxorubicin Against Drug-Resistant Cancer Cells
title_fullStr Synthesis and Biological Activities of a 3′-Azido Analogue of Doxorubicin Against Drug-Resistant Cancer Cells
title_full_unstemmed Synthesis and Biological Activities of a 3′-Azido Analogue of Doxorubicin Against Drug-Resistant Cancer Cells
title_short Synthesis and Biological Activities of a 3′-Azido Analogue of Doxorubicin Against Drug-Resistant Cancer Cells
title_sort synthesis and biological activities of a 3′-azido analogue of doxorubicin against drug-resistant cancer cells
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3317735/
https://www.ncbi.nlm.nih.gov/pubmed/22489175
http://dx.doi.org/10.3390/ijms13033671
work_keys_str_mv AT yushuwen synthesisandbiologicalactivitiesofa3azidoanalogueofdoxorubicinagainstdrugresistantcancercells
AT zhangguisheng synthesisandbiologicalactivitiesofa3azidoanalogueofdoxorubicinagainstdrugresistantcancercells
AT zhangwenpeng synthesisandbiologicalactivitiesofa3azidoanalogueofdoxorubicinagainstdrugresistantcancercells
AT luohuanhua synthesisandbiologicalactivitiesofa3azidoanalogueofdoxorubicinagainstdrugresistantcancercells
AT qiuliyun synthesisandbiologicalactivitiesofa3azidoanalogueofdoxorubicinagainstdrugresistantcancercells
AT liuqingfeng synthesisandbiologicalactivitiesofa3azidoanalogueofdoxorubicinagainstdrugresistantcancercells
AT sunduxin synthesisandbiologicalactivitiesofa3azidoanalogueofdoxorubicinagainstdrugresistantcancercells
AT wangpenggeorge synthesisandbiologicalactivitiesofa3azidoanalogueofdoxorubicinagainstdrugresistantcancercells
AT wangfengshan synthesisandbiologicalactivitiesofa3azidoanalogueofdoxorubicinagainstdrugresistantcancercells