In Silico and In vitro Investigation of the Antibacterial Potential of Substituted Aminonitriles

Aminonitriles are important synthetic intermediates widely used in the development of compounds with potential antibacterial activity. Previous studies have demonstrated antimicrobial activity in some representatives of this chemical class, suggesting that these compounds may exhibit intrinsic antibacterial properties. Considering the growing global concern regarding antimicrobial resistance, the search for new substances capable of combating resistant microorganisms has become increasingly important. Therefore, this study aimed to investigate the in silico and in vitro antibacterial potential of synthetic aminonitriles. The in silico analysis predicted activities related to the treatment of phobic disorders, inhibition of ubiquinol-cytochrome c reductase, and inhibition of membrane permeability. In the in vitro assays, antibacterial activity was identified by the microdilution method, with Minimum Inhibitory Concentrations (MICs) of 512 μg/mL, 128 μg/mL, and 512 μg/mL for HAN-1, HAN-3, and HAN-8 against Enterococcus faecalis, Staphylococcus epidermidis, and Staphylococcus aureus, respectively.

The molecules used in the in silico assays were converted into SMILES format using Discovery Studio software and analyzed using the PASS Online platform to predict their potential biological activities. The in vitro evaluation initially employed the disk diffusion method to assess inhibition halo formation. Subsequently, broth microdilution assays were performed to determine the minimum inhibitory concentrations of the aminonitriles against grampositive strains (Staphylococcus epidermidis ATCC 12228, Staphylococcus aureus ATCC 25923, and Enterococcus faecalis ATCC 29212) and gram-negative strains (Pseudomonas aeruginosa ATCC 27853, Proteus mirabilis ATCC 25933, and Escherichia coli ATCC 25922).

Computational analyses identified the main predicted bioactivities as treatment of phobic disorders, inhibition of ubiquinol-cytochrome-c reductase, and inhibition of membrane permeability. In the in vitro assays, antibacterial activity against S. epidermidis, S. aureus, and E. faecalis was detected using the microdilution technique.

This study presents a comparative evaluation of the in silico and in vitro antibacterial potential of seven aminonitrile derivatives. Although the in silico analyses suggested potential biological activities, the in vitro assays demonstrated limited antibacterial activity against the tested strains.

Some aminonitrile derivatives demonstrated potential biological activities, particularly regarding predicted pharmacological activities and bacteriostatic effects against selected Grampositive bacteria. Therefore, further investigations are necessary to better understand their mechanisms of action and explore their therapeutic potential.