Steroids are a widespread class of natural organic compounds exhibiting important and diverse biological, chemical and pharmaceutical applications. Structural changes in the steroid skeleton can lead to the development of novel synthetic derivatives with anticancer activity. For instance, the introduction of scaffolds possessing heteroatoms into the steroid nucleus represents a useful strategy for the development of new anticancer agents. Therefore, here we present the synthesis of new 2-cyanoacetohydrazide derivatives in both 17a-homo lactone and 17α-picolyl series, from the corresponding androst-4-en-3-ones as precursors. New derivatives were characterized by spectroscopic data.

In silico determination of physicochemical and ADMET properties were performed using SwissADME and ProTox-II web tools. Oral bioavailability radar provides the first information on whether a compound possesses desirable drug features, based on six physico-chemical properties of the compound: lipophilicity, size, polarity, solubility, flexibility and saturation. According to this, all parameters for both synthesized compounds are in the optimal range. The BOILED-Egg model predicts gastrointestinal absorption of both synthesized compounds, but not passage through the blood-brain barrier. The predicted toxicity of the synthesized compounds indicates that both androstane derivatives do not have mutagenic and carcinogenic potential, but they possess immunotoxic potential.

Based on in silico ADMET analysis, it can be concluded that both steroid 2-cyano-N'-acetohydrazide derivatives possess desirable drug properties with a satisfactory safety profile and that they are candidates for further in vitro tests.