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

Abstract

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 <b>TD4</b> exerted the most potent antibacterial activity against a number of <i>Staphylococcus aureus</i> (<i>S. aureus</i>), including the methicillin-resistant <i>Staphylococcus aureus</i> (MRSA), <i>Staphylococcus epidermidis</i> and <i>Enterococcus faecalis</i> strains, with the minimum inhibitory concentration (MIC) at 2-16 µg/mL. It inhibited the MRSA growth curve in a dose-dependent manner and reduced the colony formation unit in 4× MIC within 4 h. Under the transmission electron microscope, <b>TD4</b> 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 <b>TD4</b> is a potential lead compound for the development of novel antibacterial agent against the MRSA infection.