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

Area of Science:

• Medicinal Chemistry
• Computational Chemistry
• Microbiology

Background:

• Antibiotic resistance is a growing global health concern, necessitating novel drug discovery.
• Sulfur-containing compounds, both natural and synthetic, have a long history of use as antibiotics.
• The development of new antibacterial agents is crucial to combat resistant pathogens.

Purpose of the Study:

• To synthesize and evaluate the antibacterial activity of three novel thiosulfonates.
• To investigate the mechanism of action of these compounds using theoretical studies.
• To establish a structure-activity relationship for the designed thiosulfonates.

Main Methods:

• Synthesis of three thiosulfonates: S-ethyl 4-aminobenzene-1-sulfonothioate (1), S-methyl 4-acetamidobenzene-1-sulfonothioate (2), and S-ethyl 4-acetamidobenzene-1-sulfonothioate (3).
• Antibacterial activity testing against Gram-positive *Staphylococcus aureus* and Gram-negative *Escherichia coli*.
• Density Functional Theory (DFT) calculations to explore biochemical mechanisms and structure-activity relationships.

Main Results:

• Compounds 1-3 exhibited antibacterial activity against both *Staphylococcus aureus* and *Escherichia coli*.
• A proposed mechanism of action was investigated using DFT.
• A direct correlation was found between specific NBO parameters, S-S bond energy, and the antibacterial efficacy of compounds 1-3.

Conclusions:

• The novel thiosulfonates demonstrate promising antibacterial properties.
• DFT analysis provides insights into the structure-activity relationship, supporting the proposed mechanism.
• These findings can guide the future design of effective sulfur-containing antibiotics to address resistance.