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

Synthesis and properties of poly(DEX-GMA/AAc) microgel particle as a hemostatic agent.

Immediate hemorrhage control without secondary injury is pivotal for saving lives. In this study, polymerized glycidyl methacrylate derivative dextran/acrylic acid (poly(DEX-GMA/AAc)) microgel particles were prepared via emulsion polymerization method as a hemostatic agent. Microgel particles with size distribution of 500-800 nm were chosen because they showed more appropriate characteristics of swelling ratio and gelation time. The results revealed that the microgel particles had excellent swelling ratio of 68.95 g g-1 (w/w), which was 8.4 times that of counterpart clinically used microporous polysaccharide hemospheres, Arista. And poly(DEX-GMA/AAc) showed very short gelation time of 10-13 s. As a result, a gelled film could be formed rapidly after poly(DEX-GMA/AAc) absorbed water in blood when used on wounds, and then staunched bleeding. Poly(DEX-GMA/AAc) microgel particles showed better clotting ability than commercial hemostatic agent Flashclot in vitro. In addition, poly(DEX-GMA/AAc) did not cause exothermic burn when absorbing liquid, which was superior to Flashclot. No obvious toxicity was found in cytotoxicity study and skin irritancy test. Blood loss and hemostasis time were dramatically reduced by poly(DEX-GMA/AAc) microgel particles in hemorrhage models of ear vein, ear artery, liver and femoral artery in rabbits. These results indicated that the poly(DEX-GMA/AAc) microgel particles are a potential hemostatic agent with almost no cytotoxicity and good biocompatibility.