Exploring Triazole-Connected Steroid-Pyrimidine Hybrids: Synthesis, Spectroscopic Characterization, and Biological Assessment

Molecules originating from natural sources are physicochemically and biologically diverse. The conjugation of two active biomolecules has become the foundation for medical and pharmaceutical sciences. An effective synthesis of 11 new steroid-pyrimidine conjugates containing 1,2,3-triazole rings was carried out. The group of 3α-OH bile acids (lithocholic, deoxycholic, cholic) and 3β-OH sterols (cholesterol, cholestanol) were respectively modified to azidoacetates. 2-thiouracil was converted into N(1)S and N(3)S dipropargyl derivatives. Azide-alkyne cycloaddition in the presence of copper(I) of the obtained compounds led to the preparation of 1,2,3-triazole derivatives. Based on a series of spectroscopic (¹H NMR, ¹³C NMR, Fourier-transform infrared (FT-IR)), spectrometric analyses (Electrospray ionization-mass spectrometry (ESI-MS), electron impact-mass spectrometry (EI-MS)), and semiempirical calculations, the structures of all compounds were confirmed. <i>In silico</i> biological tests and molecular docking (for domain 1KZN, 2H94, 5V5Z, 1EZF, 2Q85) were performed for selected compounds. The tests performed indicate the theoretical antimicrobial potential of the obtained ligands.