Background: Steroids play an important role in life because they can regulate
a variety of biological processes and have been widely used in medicine namely as antiinflammatory,
anabolic, contraceptives and anticancer drugs. In recent years, there has
been an increasing interest in the introduction of the oxime group in a large variety of
molecules in order to increase their biological effects. This review highlights steroidal
oximes with anticancer properties and their potential mechanisms of action, as well as
data on their relative potencies reported in literature in the last few years.
Methods: To prepare this review, an extensive literature search was performed on three
databases, PubMed, ISI Web of Knowledge and Science Direct, to generate a critical but
comprehensive overview of the potential antitumor activities of steroidal oximes. The
main keywords used for the search consisted of combinations of the following terms or
their synonyms: steroidal oximes, anticancer activity and enzymatic inhibitory activity.
The abstracts and full texts were evaluated for their clarity and scientific merit and to further
help on the selection of other articles.
Results: Over the last decades the introduction of oxime groups in the steroid scaffold is
originating molecules with relevant antitumor activities, as well as steroid sulfatase, aromatase,
17α-hydroxylase-17,20-lyase, 5α-reductase and 17β-hydroxysteroid dehydrogenase
type 1 inhibitory activities. As relevant examples, pregnenolone 20-oximes
showed high activity as 17α-hydroxylase-17,20-lyase and 5α-reductase inhibitors and the
introduction of an oxime group at C-6 in androstane series also led to relevant results as
aromatase inhibitors. Interestingly, the introduction of this functional group frequently
improves the bioactivity when compared with non-oxime analogous compounds, which
can be due to extra interactions with biological targets. In addition, it has been observed
that varying the position of the hydroximino group on the parent skeleton leads to remarkable
changes in the antitumor activity.
Conclusion: The recent advances in synthesis and in vitro bioactivity studies of steroidal
oximes contributed to understand the potential interest of the introduction of this functional
group in the steroidal nucleus in the development of anticancer molecules. Moreover,
the cytotoxic/enzyme inhibitory activity usually depends on the position of the oxime
group in different steroid scaffolds. However, despite the promising results, it is necessary
to perform more in vitro and in vivo assays not only to better explore the mechanisms of
action but also to confirm the potential effectiveness and safety of this interesting family
of compounds in clinical practice.