Amides of antibiotic streptonigrin and amino dicarboxylic acids or aminosugars. Synthesis and biological evaluation.

Streptonigrin has been shown to be a potent cytotoxic agent, with broad spectrum activity in a number of murine tumor models1\ Recently it was shown that streptonigrin is a nonintercalative antibiotic, which induces mammaliantopoisomerase II dependent DNAcleavage2). It is a strong inhibitor of the reverse transcriptase associated with avian myeloblastosis virus and humanimmunodeficiency virus3). However, the severe side effects of streptonigrin, mainly bone marrow depression, have resulted in the discontinuation of its clinical use as an antitumor compound. Here we report on the preparation and biological evaluation of the amides of streptonigrin and amino dicarboxylic acids or aminosugars, which may be of interest, as they should be more water-soluble and possibly less toxic. In the synthesis of streptonigrin amides we used the iV-hydroxysuccinimide ester of streptonigrin (2), which represents a convenient agent for the preparation of poly functional derivatives as in this case there is no need to protect hydroxy groups of aminosugars. Streptonigrin (1) and iV-hydroxysuccinimide in THF in the presence of DCCprovided 2 (Tables 1 and 2). 2 was purified by column chromatography JUNE 1992