In silico Evaluation of the Antibacterial Potential of the Cyclic Tetrapeptide Tentoxin Derived from Alternaria alternate.

Abstract

Introduction/objective: The main objective of this study is to test in silico the previously unexplored antimicrobial activity of the tetrapeptide tentoxin. To investigate its efficacy, in silico molecular docking was performed to analyze its interactions with key resistancerelated proteins, specifically FusB and the bacterial IMPDH, a validated target for antibiotic development.

Methods: Ligand preparation and quantum chemical analysis of tentoxin were performed using DFT at the CAM-B3LYP/TZVP level of theory. Molecular docking was executed via Auto- DockVina, while ADMET profiles were predicted using the Deep-PK platform. Protein-ligand interactions were characterized through computational visualization tools to assess binding modes and stability.

Results: For FusB, a binding energy of -9.1 kcal/mol with an inhibition constant of 0.213 μM was obtained. For bacterial IMPDH, a binding energy of -7.3 kcal/mol with an inhibition constant of 4.449 μM was obtained.

Discussion: These findings represent the first evidence of tentoxin's potential as a bacterial inhibitor. The strong binding to FusB and IMPDH suggests a specific mechanism of action, confirming that the compound effectively targets key bacterial proteins.

Conclusion: These results provide a theoretical foundation for subsequent in vitro studies of tentoxin against a broad spectrum of bacteria, including multidrug-resistant strains. Our findings highlight the potential of natural fungal metabolites as a scaffold for developing novel antibacterial agents.