Document Detail

Synthesis and biological activities of a 3'-azido analogue of Doxorubicin against drug-resistant cancer cells.
MedLine Citation:
PMID:  22489175     Owner:  NLM     Status:  In-Data-Review    
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.
Shuwen Yu; Guisheng Zhang; Wenpeng Zhang; Huanhua Luo; Liyun Qiu; Qingfeng Liu; Duxin Sun; Peng-George Wang; Fengshan Wang
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Publication Detail:
Type:  Journal Article     Date:  2012-03-19
Journal Detail:
Title:  International journal of molecular sciences     Volume:  13     ISSN:  1422-0067     ISO Abbreviation:  Int J Mol Sci     Publication Date:  2012  
Date Detail:
Created Date:  2012-04-10     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101092791     Medline TA:  Int J Mol Sci     Country:  Switzerland    
Other Details:
Languages:  eng     Pagination:  3671-84     Citation Subset:  -    
School of Pharmaceutical Sciences, Shandong University, Jinan 250012, China; E-Mail:
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