Steroid-linked nitrogen mustards as potential anticancer therapeutics: a review

Abstract

Nitrogen mustards, an important class of drugs for cancer therapy, are known as DNA alkylating agents. The nitrogen mustards are highly reactive and, as a consequence, lack of selectivity and produce several adverse side effects. In order to minimize these undesirable effects, the attachment of nitrogen mustards to a steroidal hormone with affinity for its receptor can lead to highly selective and less toxic antineoplastic therapeutics. This review will focus on the design, synthesis and evaluation of such steroid-nitrogen mustard hybrids as antineoplastic agents. Among these compounds, modified steroids with aromatic nitrogen mustards linked by an ester function were found to have better DNA alkylating properties, improved selectivity as well as low toxicity. This article is part of a Special Issue entitled "Synthesis and biological testing of steroid derivatives as inhibitors".

Keywords: 4-Me-CABA; ACA; ADR; Anticancer agents; BCNU; CHL; CNC; CP; DTIC; DnsEM; EM; EMP; ER; EoM; HASE; ILS; LDL; MN; MNU; MeCCNU; Nitrogen mustard; PC; PHE; PHO; PRIs; RBA; SCEs; SMART; Steroid; Steroid-nitrogen mustard hybrids; adriamycin; aminocinnamic acid; carmustine; chlorambucil or para-[N,N-bis(2-chloroethyl)amino]phenylbutyric acid; chloronitrocarbamoyl; cisplatin; dacarbazine; dansyl estramustine; estramustine; estramustinephosphate; estrogen receptor; estromustine; homo-aza-steroidal alkylating ester; increase in lifespan; low-density lipoproteine; methylnitrosourea; micronuclei; para-[N,N-bis(2-chloroethyl)amino]phenoxy acetic acid; para-[N,N-bis(2-chloroethyl)amino]phenylacetic acid; para-methyl-meta-[N,N-bis(2-chloroethyl)amino]benzoic acid; proliferation rate indices; prostate cancer; rLDL; reconstituted-LDL; relative binding affinity; semustine; sister chromatid exchanges; somatic mutation and recombination test.