9-ALKYL, MORPHOLINYL ANTHRACYCLINES IN THE CIRCUMVENTION OF MULTIDRUG RESISTANCE

The intramolecular combination of 9-alkyl substitution in the anthracyline 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. © 1990.