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The highly lipophilic cyanomorpholinyl adriamycin (CMA) is the most potent antineoplastic anthracycline yet described. CNS distribution and toxicity were examined after i.v. administration of CMA to mice. At doses greater than or equal to 0.1 mg/kg, a neurotoxic syndrome including ataxia, hypokinesia, and tremors appeared. At doses of less than or equal to 0.05 mg/kg, which have been reported to be antineoplastic, no neurotoxicity was observed. On histopathologic examination, no changes were observed in the brain, spinal cord, or dorsal root ganglia. Unlike adriamycin (ADR), which rapidly appears in the nuclei of several tissues, CMA showed no fluorescence, suggesting a different cellular microcompartmentalization. The i.d. injection of CMA disclosed a 200-fold increase in toxicity compared with that of adriamycin. In comparisons of CMA and ADR, neurotoxicity and cardiotoxicity occurred equally only at higher doses; however, the dermatotoxicity and antineoplastic activity of CMA were increased several hundred-fold.

We have confirmed that doxorubicin induces irreversible changes in the nucleolar ultrastructure of myocardial cells of rats. Similar changes were not caused by an equal dose of the synthetic analogue, 5-iminodaunomycin. These results combined with previous and current comparative tests with this analogue, doxorubicin, and daunomycin suggest that 5-iminodaunomycin may serve as a less cardiotoxic anthracycline derivative.

Viene confermato che la struttura dell'agente dolcificante perillartina e quella di unasim ossima. Il tentativo di ottenere l'isomeroanti per azione dell'acido cloridrico ha condotto invece all'addotto tra HCl e gruppo isopropenilico, mentre il trattamento con trifluoruro di boro ha provocato solo la migrazione del doppio legame per formare l'analogo derivato dell'1, 3-cicloesadiene.