Synthesis and Characterization of Natural Product-Based Steroid-Triazole Hybrids via Click Reaction and Evaluation of Their Anticancer and Antibacterial Activities

Two highly significant classes of natural and heterocyclic compounds, steroids and triazoles, are pivotal in numerous biological processes, and several steroid conjugates and triazole hybrids exhibiting anticancer and antibacterial activities were reported. In this work, a series of 47 new triazoles based on steroid moieties were synthesized via click chemistry. The effective click reaction of steroid propargyl ethers and steroid acetylenic esters with aryl azides provided quantitative yields of the desired steroid-triazole conjugates. The new compounds were fully characterized based on spectral data, including NMR, HRMS, FT-IR, and single X-ray diffraction analysis. The biological activity of the new steroid-triazole hybrids was evaluated through assessments of their anticancer and antibacterial activities. The screen identified three hits with selective antibacterial activity against the Gram-positive <i>Staphylococcus aureus</i> (MIC 12.5-50 μM; IC₅₀ 8.9-41.5 μM), and one compound was weakly cytotoxic against the triple-negative breast cancer cells MDA-MB-231.