## 1 Introduction  
One strategy for the synthesis of compounds with potential pharmacological applications is to use biologically active compounds as starting materials. Modifications of naturally occurring compounds with established biological activity, such as steroids and alkaloids, exemplified this approach. Steroids are one of the most important classes of natural compounds. These include hormones, pheromones, sterols, and bile acids. Bile acids, e.g., lithocholic acid, deoxycholic acid as well as cholic acid, are the primary metabolites of cholesterol in the form of polyhydroxylated steroids. The specific skeleton geometry and hydroxyl groups of the bile acids (\(3\alpha\) or \(3\alpha\), \(12\alpha\), and also \(3\alpha\), \(7\alpha\), \(12\alpha\)) play a significant role in their amphiphilic properties. These compounds and their derivatives have led to their application in many fields of chemistry, such as molecular recognition, biomimetic chemistry, host-guest chemistry, and pharmacology [1, 2, 3]. Moreover, bile acids have found applications as building blocks in the synthesis of molecular receptors; their dimers are infused in synthesizing macrocyclicartificial receptors with good organogelling properties [4; 5; 6; 7; 8; 9; 10]. At the same time, cholesterol and cholestanol as sterols have a secondary hydroxyl group in the steroid skeletons at the C-3 position. Within this class of compounds, they also differ in modifying the side chains or the presence of double bonds [11; 12; 13]. Among the alkaloids, indole and purine compounds are particularly noteworthy. Indole compounds display a range of biological activities. They have been shown to have anti-inflammatory [14], antioxidant [15] and anticancer [15; 16] effects. Of particular interest is the naturally occurring indole alkaloid gramine. Its broad spectrum of biological activity and ease of modification make it the starting point for many syntheses [17]. Gramine and its derivatives have various properties ranging from antiviral [18] and anticancer [19] to insecticidal [20] and anticorrosive [21]. They also reduce the toxicity of cholic acid to human erythrocytes [22; 23]. Another alkaloid that has attracted the attention of scientists is caffeine. It has stimulating [24], antibacterial [25] and antifungal [26] effects. Caffeine derivatives in which the substituent is located at the C-8 position are particularly interesting for their antioxidant activity [27; 28]. They are also monoamine oxidase (MAO) inhibitors, which significantly increase their potential in the fight against neurodegenerative diseases such as Alzheimer's and Parkinson's [29; 30]. Sulfur derivatives of caffeine are potential anticancer agents [31]. These compounds also exhibit significant antibacterial activity, making them promising candidates for the development of new antibiotics, especially in the face of increasing resistance to traditional antibiotics [32]. Both caffeine and gramine have been used to synthesize hybrid compounds. An interesting example of a caffeine hybrid is the combination of caffeine with Eddystone D. This unique combination results in a compound with a higher affinity for adenosine receptors than caffeine alone [33]. Gramine-uracil and gramine-imidazole hybrids show cytoprotective effects against AAPH-induced oxidative hemolysis [34; 35]. Steroid-gramine bioconjugates with a triazole linker are examples of hybrids with potential antibacterial and antifungal activity [36]. In view of the above, we plan to synthesize the unique steroid-gramine bioconjugates and evaluate their pharmacological activities using the in silico program PASS (Pharma Expert Predictive Services (@2011-2013, Version 2.0. ), a widely accepted tool for predicting biological activities. The lack of literature reports on the synthesis of caffeine-steroid hybrids prompted us to extend our studies to the caffeine molecule. Considering the promising potential of the new compounds as biologically active agents, their selected biological activity was evaluated using molecular docking methodology.