Synthesis and evaluation of new steroidal lactam conjugates with aniline mustards as potential antileukemic therapeutics

•Novel azasteroidal alkylating esters were synthesized as antileukemic agents.•The azasteroidal alkylating esters were tested for antileukemic activity in vitro and in vivo.•The alkylating esters were compared to melphalan and POPAM.•The azasteroidal alkylators showed low acute toxicity.•The tested compounds exhibit promising antileukemic activity both in vitro and in vivo.

Alkylating agents are still nowadays one of the most important classes of cytotoxic drugs, which display a wide range of therapeutic use for the treatment of various cancers. We have synthesized and tested four hybrid homo-azasteroidal alkylating esters for antileukemic activity against five sensitive to alkylating agents human leukemia cell lines in vitro and against P388 murine leukemia in vivo. Comparatively, melphalan and 3-(4-(bis(2-chloroethyl)amino)phenoxy)propanoic acid (POPAM) were also examined. All the homo-aza-steroidal alkylators showed relatively lower acute toxicity, very promising and antileukemic activity both in vitro and in vivo.

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