Antitumor anthracycline antibiotics. Structure-activity and structure-cardiotoxicity relationships of rubidazone analogs

Abstract

Rubidazone analogues with varying phenyl group sibstituents was prepared. The effect of these compounds on inhibition of nucleic acid synthesis in cultured [mouse P-388 lymphocytic leukemia] cells, on in vivo antitumor properties and on cardiotoxicity [in rats] was examined. Substituent effects on drug-DNA binding as indicated by [calf] DNA melting temperature measurements were also investigated. Substituent effects were essentially absent among the rubidazone analogues in vivo and in vitro test systems which measure cytotoxic characteristics; the rubidazone analogues varied substantially in their cardiotoxic effects and this variation was closely correlated with the electronic character of the phenyl substituent.