title: Preparation and antitumor activity of a tamibarotene-furoxan derivative.
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.
authors.affiliation: School of Pharmacy and Biology Science, Weifang Medical University, Weifang, China E-mail : zhangtao226@163.com, wxj2901@126.com.
authors.forename: Xue-Jian
authors.initials: XJ
authors.lastname: Wang
authors.forename: Yu
authors.initials: Y
authors.lastname: Duan
authors.forename: Zong-Tao
authors.initials: ZT
authors.lastname: Li
authors.forename: Jin-Hong
authors.initials: JH
authors.lastname: Feng
authors.forename: Xiang-Po
authors.initials: XP
authors.lastname: Pan
authors.forename: Xiu-Rong
authors.initials: XR
authors.lastname: Zhang
authors.forename: Li-Hong
authors.initials: LH
authors.lastname: Shi
authors.forename: Tao
authors.initials: T
authors.lastname: Zhang
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology*; D001565:Benzoates / Q000737:chemistry* / Q000494:pharmacology; D015153:Blotting, Western; D049109:Cell Proliferation / Q000187:drug effects*; D005260:Female; D006801:Humans; D007938:Leukemia / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008819:Mice, Nude; D008956:Models, Chemical; D009569:Nitric Oxide / Q000378:metabolism; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D010069:Oxadiazoles / Q000138:chemical synthesis* / Q000737:chemistry* / Q000494:pharmacology*; D018168:Receptors, Retinoic Acid / Q000378:metabolism; D013764:Tetrahydronaphthalenes / Q000138:chemical synthesis* / Q000737:chemistry* / Q000494:pharmacology*; D014407:Tumor Cells, Cultured; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D001565:Benzoates; D010069:Oxadiazoles; C000613608:QT-011; D018168:Receptors, Retinoic Acid; D013764:Tetrahydronaphthalenes; C010166:furoxans; C061133:tamibarotene; D009569:Nitric Oxide