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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Antineoplastic Agents / chemical synthesis*
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Antineoplastic Agents / pharmacology*
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Benzoates / chemistry*
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Benzoates / pharmacology
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Blotting, Western
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Cell Proliferation / drug effects*
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Female
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Humans
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Leukemia / drug therapy*
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Leukemia / metabolism
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Leukemia / pathology
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Mice
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Mice, Nude
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Models, Chemical
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Nitric Oxide / metabolism
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Ovarian Neoplasms / drug therapy*
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Ovarian Neoplasms / metabolism
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Ovarian Neoplasms / pathology
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Oxadiazoles / chemical synthesis*
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Oxadiazoles / chemistry*
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Oxadiazoles / pharmacology*
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Receptors, Retinoic Acid / metabolism
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Tetrahydronaphthalenes / chemical synthesis*
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Tetrahydronaphthalenes / chemistry*
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Tetrahydronaphthalenes / pharmacology*
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Tumor Cells, Cultured
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Xenograft Model Antitumor Assays
Substances
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Antineoplastic Agents
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Benzoates
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Oxadiazoles
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QT-011
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Receptors, Retinoic Acid
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Tetrahydronaphthalenes
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furoxans
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tamibarotene
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Nitric Oxide