期刊论文详细信息
International Journal of Molecular Sciences
Synthesis and Biological Activities of a 3'-Azido Analogue of Doxorubicin Against Drug-Resistant Cancer Cells
Shuwen Yu3  Guisheng Zhang2  Wenpeng Zhang4  Huanhua Luo1  Liyun Qiu1  Qingfeng Liu2  Duxin Sun5  Peng-George Wang4 
[1] Jinan Central Hospital Affiliated to Shandong University, Jinan 250011, China; E-Mails:;College of Chemistry and Environmental Sciences, Henan Normal University, Xinxiang 453002, China; E-Mails:;School of Pharmaceutical Sciences, Shandong University, Jinan 250012, China; E-Mail:;Department of Chemistry and Biochemistry, The Ohio State University, Ohio 43210, USA; E-Mail:;College of Pharmacy, The University of Michigan, Michigan 48109, USA; E-Mail:
关键词: anthracycline;    Azido;    multidrug resistance;    ADOX;    P-gp;   
DOI  :  10.3390/ijms13033671
来源: mdpi
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【 摘 要 】

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.

【 授权许可】

CC BY   
© 2012 by the authors; licensee Molecular Diversity Preservation International, Basel, Switzerland.

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