Biological evaluation and molecular docking studies of novel aza-acyclic nucleosides as putative antimicrobial, anticancer, and antioxidant agents.

This study aimed to synthesize new aza-acyclic nucleosides (aza-acyclovir) and evaluate the efficacy of these synthetic compounds as potential antimicrobial, anticancer, and antioxidant agents. We prepared two novel aza-acyclic nucleosides via two reactions. The first reaction involved trichloroisocyanuric acid and dibenzosulphonyl diethylamine, and the second reaction involved trichloroisocyanuric acid and diethanolamine. We then used one-dimensional nuclear magnetic resonance (NMR) spectroscopy, two-dimensional NMR spectroscopy, infrared spectroscopy, and mass spectrometry to determine the structures of the resulting compounds. In this regard, we first tested the antimicrobial activity of these compounds against various bacteria, including Bacillus cereus, B. subtilis, Staphylococcus epidermidis, Staphylococcus aureus, Escherichia coli, Proteus mirabilis, and Pseudomonas aeruginosa, and against fungal pathogens, including Aspergillus fumigatus, Candida tropicalis, and Alternaria solani. Next, the precise mode for the interaction between synthesized aza-acyclic nucleosides and the target protein 8HQ5 was elucidate using molecular docking analysis. Subsequently, we tested the synthesized compounds for putative anticancer activity at different concentrations (i.e., 12.5, 25, 50, 100, and 200 µg/mL) against A549 cell (Human epithelial lung carcinoma) and human umbilical vein endothelial cell (HUVEC) lines. In addition, compounds antioxidant activity was evaluated using the 2,2-diphenyl-1-picrylhydrazyl-based and cupric reducing antioxidant capacity-based methods at different concentrations (i.e., 31.25, 62.5, 125, 250, and 500 µg/mL). Results revealed that both aza-acyclic nucleosides inhibited both bacterial and fungal strains, although toxicity toward bacterial strains was generally greater than toward fungal strains. We also observed that the molecular docking results were consistent with the results of in vitro antimicrobial assessments. Further, both aza-cyclic nucleosides exhibited cytotoxic effects against both the A549 cell and HUVEC lines. Despite exhibiting lower radical scavenging activity than ascorbic acid (an antioxidant compound used as a standard), Compound 1 from the novel synthetic aza-acyclic nucleosides showed a higher reduction capacity, which was dose-dependent. Overall, we report newly synthesized compounds that show promising antimicrobial, anticancer, and antioxidant effects.