Abstract
The intramolecular combination of 9-alkyl substitution in the anthracycline A-ring plus incorporation of the amino group of the daunosamine sugar within a morpholinyl ring led to the retention of almost complete activity against P-glycoprotein positive, multidrug resistant variants of a mouse mammary tumour line and a human small cell lung cancer line. Resistance factors were close to unity. These structural elements may prevent efflux by the P-glycoprotein multidrug transporter. The use of 9-alkyl, morpholinyl anthracyclines with resistance circumvention properties may have clinical application.
MeSH terms
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ATP Binding Cassette Transporter, Subfamily B, Member 1
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Aclarubicin / analogs & derivatives
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Aclarubicin / therapeutic use
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Adjuvants, Immunologic / therapeutic use
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Animals
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Antibiotics, Antineoplastic / therapeutic use*
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Carcinoma, Small Cell / drug therapy
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Doxorubicin / analogs & derivatives*
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Doxorubicin / therapeutic use
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Drug Resistance
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Humans
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Lung Neoplasms / drug therapy
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Mammary Neoplasms, Experimental / drug therapy
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Membrane Glycoproteins / analysis
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Mice
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Neoplasm Proteins / analysis
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Tumor Cells, Cultured / drug effects
Substances
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ATP Binding Cassette Transporter, Subfamily B, Member 1
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Adjuvants, Immunologic
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Antibiotics, Antineoplastic
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Membrane Glycoproteins
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Neoplasm Proteins
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aclacinomycins
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Aclarubicin
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Doxorubicin
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NSC 354646
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3'-deamino-3'-(3-cyano-4-morpholinyl)doxorubicin