Synthesis, characterization, and antibacterial activity of novel hybrid purine-triazole Schiff base derivatives

In the discovery of novel antibiotics, a new series of Schiff base purine derivatives (7-11) was synthesized from two newly prepared purine ring-containing aldehydes (6a) and (6b). The newly synthesized compounds incorporated three bioactive fragments, namely purine, triazole, and the azomethine group. The structures of the synthesized Schiff bases and their corresponding aldehyde precursors were elucidated and confirmed using ¹H and ¹³C NMR spectra and HRMS. The antibacterial activity of the newly synthesized compounds was evaluated against four bacteria: two gram-positive (Staphylococcus Aureus and Enterococcus faecalis) and two gram-negative bacteria (Escherichia coli and Pseudomonas aeruginosa). Among the tested compounds, aldehyde (6b) exhibited the most potent activity against S. aureus (MIC = 200 μg/mL), while Schiff bases (8-10) were most effective against P. aeruginosa (MIC = 200 μg/mL). Additionally, compound (11) demonstrated notable activity against E. coli and E. faecalis (MIC = 390 μg/mL and 200 μg/mL, respectively). To gain further insight into the antibacterial potential of these compounds, molecular docking studies were conducted to investigate their interactions with key bacterial proteins essential for their viability. As a result, compounds 6a and 7 exhibited the highest binding affinities among all tested molecules, showing strong interactions with almost all selected target proteins, including E. coli (4URO), S. aureus (4CJN), and E. faecalis (2Z1P and 6ORI). Compound 6a demonstrated remarkable binding, with affinities of -8.7 kcal/mol for E. faecalis (2Z1P) and - 9.9 kcal/mol for E. faecalis (6ORI). Similarly, compound 7 displayed high affinities of -8.4 kcal/mol with E. faecalis (2Z1P) and - 9.0 kcal/mol with P. aeruginosa (2UV0).