9-Alkyl, morpholinyl anthracyclines in the circumvention of multidrug resistance.

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.

• Authors: H M Coley, P R Twentyman, P Workman
• Journal: European journal of cancer (Oxford, England : 1990) (Eur J Cancer) Vol. 26 Issue 6 Pg. 665-7 ( 1990) ISSN: 0959-8049 [Print] England
• PMID: 1975502 (Publication Type: Journal Article)

Chemical References

• ATP Binding Cassette Transporter, Subfamily B, Member 1
• Adjuvants, Immunologic
• Antibiotics, Antineoplastic
• Membrane Glycoproteins
• Neoplasm Proteins
• aclacinomycins
• Aclarubicin
• Doxorubicin
• NSC 354646
• 3'-deamino-3'-(3-cyano-4-morpholinyl)doxorubicin

Topics

• ATP Binding Cassette Transporter, Subfamily B, Member 1
• Aclarubicin (analogs & derivatives, therapeutic use)
• Adjuvants, Immunologic (therapeutic use)
• Animals
• Antibiotics, Antineoplastic (therapeutic use)
• Carcinoma, Small Cell (drug therapy)
• Doxorubicin (analogs & derivatives, therapeutic use)
• Drug Resistance
• Humans
• Lung Neoplasms (drug therapy)
• Mammary Neoplasms, Experimental (drug therapy)
• Membrane Glycoproteins (analysis)
• Mice
• Neoplasm Proteins (analysis)
• Tumor Cells, Cultured (drug effects)