Steroid–nucleosides possible novel agents for cancer chemotherapy

Abstract

THE major classes of anti-cancer chemotherapeutic drugs include alkylating agents, anti-metabolites of nucleic acids, steroid hormones and antibiotics¹. Because of the lack of specificity of anti-tumour agents, attempts have been made to increase their specificity and cell-penetrating properties by coupling them to steroid hormones^2,3. In particular, steroidal alkylating agents exhibit carcinostatic properties if used in combination with other modes of therapy⁴. We have prepared a novel class of agents by coupling steroids with naturally occurring purines and pyrimidines by way of a C–N linkage. The structures are unique in that they may be regarded as analogues both of steroid hormones and of ‘nucleosides’ in which the sugar has been replaced. Accordingly, we may expect their steroid moiety to provide target specificity, while their nucleoside characteristics may result in interference at the DNA level to give the desired anti-tumour activity. Preliminary studies on the effect of steroid–nucleosides on the lifespan of tumour-bearing animals show that selectively coupled products exhibit anti-tumour activity.