In Search of New Drugs: Elucidating the Activity of Structurally Similar Potential Antibiotics Using Molecular Modelling

TL;DR

This study explores the antibacterial activity of three new sulfur-containing compounds and uses molecular modeling to understand their potential as antibiotics.

Contribution

The paper introduces three new thiosulfonates and links their antibacterial activity to molecular properties using DFT analysis.

Findings

The three new thiosulfonates show antibacterial activity against Gram-positive and Gram-negative bacteria.

NBO parameters and S-S bond energy correlate with the compounds' antibacterial activity.

Theoretical studies support a proposed biochemical mechanism for the compounds' action.

Abstract

The global problem of antibiotic resistance leads to the necessity for drug improvement and discovery. Natural and synthetic sulfur-containing compounds have been known as antibiotics for many years. In the current study, we demonstrated an antibacterial activity of three new thiosulfonates: S-ethyl 4-aminobenzene-1-sulfonothioate (1), S-methyl 4-acetamidobenzene-1-sulfonothioate (2), and S-ethyl 4-acetamidobenzene-1-sulfonothioate (3). Their activities were studied on two model Gram-positive and Gram-negative bacteria strains: Staphylococcus aureus ATTC 6538P and Escherichia coli ATTC 8739, respectively. According to the literature data, we proposed a general mechanism of 1−3 biochemical actions. To analyze its feasibility, theoretical studies using density functional theory (DFT) were performed. The obtained results demonstrate a direct correlation between some NBO parameters and the S-S bond energy of 1−3 with their activity against both studied bacterial strains. The obtained results could be helpful for future biomedical studies on the analyzed compounds and promote the further design of new S-containing antibiotics.

Figures