Potential antitumor phenoxazines.
From the various studies cited, spanning more than forty years, it is clear that some members of the phenoxazine and benzophenoxazine dye family selectively stain certain tumors and, when given in suitable concentrations in the feed, can prolong life and shrink tumors. In addition, some use has been made of these compounds as carriers for other antitumor agents based upon the idea of selective accumulation into tumor tissue. Although many analogs have been made and examined, the work has been done in a relatively unfocused manner and the field could benefit from a systematic study of the effect of structure on biological activity. None of the synthetic materials prepared and tested to date has the potency of the outstanding antitumor natural products bearing the ring system of the actinomycins. Advances in our understanding of the molecular mode of action of the actinomycins, based in large measure upon x-ray studies, suggest some avenues for future exploitation. To date, attempts to prepare simplified actinomycins or elaborate phenoxazines to accomplish this have been disappointing.