Evaluation of Antibacterial Activity of Thiourea Derivative TD4 against Methicillin-Resistant Staphylococcus aureus via Destroying the NAD plus /NADH Homeostasis

To develop effective agents to combat bacterial infections, a series of thiourea derivatives (TDs) were prepared and their antibacterial activities were evaluated. Our results showed that TD4 exerted the most potent antibacterial activity against a number of Staphylococcus aureus (S. aureus), including the methicillin-resistant Staphylococcus aureus (MRSA), Staphylococcus epidermidis and Enterococcus faecalis strains, with the minimum inhibitory concentration (MIC) at 2-16 mu g/mL. It inhibited the MRSA growth curve in a dose-dependent manner and reduced the colony formation unit in 4x MIC within 4 h. Under the transmission electron microscope, TD4 disrupted the integrity of MRSA cell wall. Additionally, it reduced the infective lesion size and the bacterial number in the MRSA-induced infection tissue of mice and possessed a good drug likeness according to the Lipinski rules. Our results indicate that TD4 is a potential lead compound for the development of novel antibacterial agent against the MRSA infection.

Automated summary

A series of thiourea derivatives (TDs) were prepared and tested for their antibacterial activities, and TD4 exhibited the most potent antibacterial activity against various strains of Staphylococcus aureus (S. aureus), including methicillin-resistant Staphylococcus aureus (MRSA). It disrupted the integrity of the MRSA cell wall and showed efficacy in reducing bacterial numbers and lesion size in MRSA-induced infection in mice. These findings suggest that TD4 has potential as a lead compound for the development of novel antibacterial agents against MRSA infections.