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http://dx.doi.org/10.7314/APJCP.2014.15.15.6343

Preparation and Antitumor Activity of a Tamibarotene-Furoxan Derivative  

Wang, Xue-Jian (School of Pharmacy and Biology Science, Weifang Medical University)
Duan, Yu (School of Pharmacy and Biology Science, Weifang Medical University)
Li, Zong-Tao (Research and Development Department, Shandong Qidu Pharmaceutical Co. Ltd.)
Feng, Jin-Hong (Shandong Analysis and Test Center, Shandong Academy of Sciences)
Pan, Xiang-Po (Clinical Laboratory, Weifang People's Hospital)
Zhang, Xiu-Rong (School of Pharmacy and Biology Science, Weifang Medical University)
Shi, Li-Hong (School of Pharmacy and Biology Science, Weifang Medical University)
Zhang, Tao (Research and Development Department, Shandong Qidu Pharmaceutical Co. Ltd.)
Publication Information
Asian Pacific Journal of Cancer Prevention / v.15, no.15, 2014 , pp. 6343-6347 More about this Journal
Abstract
Multi-target drug design, in which drugs are designed as single molecules to simultaneously modulate multiple physiological targets, is an important strategy in the field of drug discovery. QT-011, a tamibarotene-furoxan derivative, was here prepared and proposed to exert synergistic effects on antileukemia by releasing nitric oxide and tamibarotene. Compared with tamibarotene itself, QT-011 displayed stronger antiproliferative effects on U937 and HL-60 cells and was more effective evaluated in a nude mice U937 xenograft model in vivo. In addition, QT-011 could release nitric oxide which might contribute to the antiproliferative activity. Autodocking assays showed that QT-011 fits well with the hydrophobic pocket of retinoic acid receptors. Taken together, these results suggest that QT-011 might be a highly effective derivative of tamibarotene and a potential candidate compound as antileukemia agent.
Keywords
Tamibarotene; NO donor; anti-tumor compound; retinoic acid receptors;
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