## 1 Introduction  
Structural modification of natural sex hormones by the introduction of various heterocyclic moieties may alter the physicochemical properties and the pharmacokinetic behavior, as well as the biological activity of the parent compound [1]. Continuous interest in steroid derivatives with nitrogen-containing heterorings condensed with, or connected to ring D of the sterane framework arises from the significant pharmacological potential of these molecules [2]. Several studies have demonstrated that steroidal aza-heterocyclic derivatives can be effective in the prevention and treatment of hormone-dependent cancers. They can also act as cytotoxic agents through hormone-independent mechanisms of action [3]. Heteroaromatic five-membered pyrazoles containing two adjacent nitrogen atoms have received considerable attention thanks to their facile synthetic availability and their usefulness as intermediates for the preparation of various biologically active compounds, metal complexes, and functional materials [4; 5]. Over the past decades, numerous pyrazoles in the androstane series and their partially saturated pyrazoline analogs have been reported to exhibit a more marked antitumor activity rather than their expected hormonal effect (Figure 1) [6; 7; 8; 9; 10; 11; 12; 13]. Amongst functionalized pyrazoles, 5-aminopyrazoles have been widely investigated as biologically active agents [14] and as useful binucleophilic precursors for fused pyrazoloazines of medicinal interest [15]. Moreover, 5-amino-1-arylpyrazoles, which are usually obtained by the reaction of \(\beta\)-ketonitriles or malonitrile derivatives with arylhydrazines, constitute the main structural motif of a vast number of bioactive compounds with kinase-inhibitory, anticancer, anti-infective, anti-inflammatory, or other effects [16]. Although \(\beta\)-ketonitriles are also suitable starting materials for the synthesis of other 5-amino-substituted 1,2-azoles, such as isoxazols [17] or isothiazoles [18], previous research has shown that the incorporation of a \(N\),\(N\)-heterocyclic ring into the sterane backbone is much more beneficial in terms of anticancer activity. As concerns the synthetic methodologies, a number of reactions have been reported so far for the synthesis of different steroid-fused heterocycles under microwave (MW) irradiation due to the advantageous characteristics of this approach, such as enhanced reaction rates, manipulative simplicity, and high product yields [19; 20].  
In view of the marked cytotoxic activity of some androstane-based pyrazol(in)es [6; 7; 8; 9; 10; 11; 12; 13], and the pharmacological relevance of drugs containing a 5-amino-1-arylpyrazole moiety [16], the aim of the present study was to introduce such heterocyclic subunit fused to ring D of dehydroepiandrosterone (DHEA) to obtain a set of compounds suitable for further investigations. To our knowledge, steroidal 5-aminopyrazoles have not been synthesized and studied so far. The heterocyclizations were designed and performed from a DHEA-derived \(\beta\)-ketonitrile and various arylhydrazines, respectively, under pre-optimized MW-assisted reaction conditions. Proton dissociation processes of the heterocycles and the dependence of the determined pK\({}_{a}\) values on the electron demand  
Figure 1: Some previously synthesized androstane-based pyrazol(in)es with anticancer activity [6; 7; 8; 9; 10; 11; 12; 13] and 5-amino-1-arylpyrazoles (framed), which are the subjects of the present study.  
of the aryl substituents were also investigated. The cytotoxicity of the molecules was screened in vitro on different human cancer cell lines, along with a noncancerous cell line by the colorimetric 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolzolium bromide (MTT) assay [21]. In addition, based on the screen, one compound--showing the highest efficacy to inhibit the proliferation of various cancer cells--was selected and subjected to additional in vitro tests in order to determine its IC\({}_{50}\) values on all tested cell lines.