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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