Abstract
A 1,2,5-tetrazole derivative (DTE) was synthesized via a ZnSO4-catalyzed [3 + 2] cycloaddition reaction between succinonitrile and sodium azide, and its structure was confirmed through experimental and theoretical approaches. The compound exhibited favorable biocompatibility in HUVEC cells, with half-maximal inhibitory concentration (IC50) values of 764.2 and 567.9 µg/mL after 24 and 48 h, respectively, indicating relatively low cytotoxicity. In vitro antibacterial assays showed moderate activity against both Escherichia coli and Staphylococcus aureus, with minimum inhibitory concentration (MIC) values of 1.5 mg/mL and minimum bactericidal concentration (MBC) values of 2.0 and 2.5 mg/mL, respectively. Fluorescence spectroscopy indicated that DTE interacts with calf thymus DNA (CT-DNA) with a more favorable binding free energy (ΔG° = - 7.94 kcal/mol) than with bovine serum albumin (BSA; ΔG° = - 6.09 kcal/mol), suggesting a stronger interaction with DNA. Computational analyses indicated that DTE is a chemically stable yet strongly electrophilic molecule (ω = 3.30 eV), with negative electrostatic potential localized on tetrazole nitrogen atoms, which likely act as key interaction sites. Absorption, distribution, metabolism, excretion, and toxicity (ADME-Tox) predictions suggested compliance with Lipinski's rule of five, absence of predicted mutagenic or tumorigenic risks, and overall acceptable drug-likeness and safety profile. In addition, molecular docking was employed to explore the potential binding sites and interactions of DTE with the macromolecular targets. Therefore, the integrated experimental and theoretical results suggest that DTE interacts primarily with DNA and may serve as a useful scaffold for further development of antimicrobial agents.