Discovery of Quaternized Pyridine-Thiazole-Pleuromutilin Derivatives with Broad-Spectrum Antibacterial and Potent Anti-MRSA Activity.

The quaternization of compounds has emerged as a promising molecular design strategy for the development of antibiotics. Herein, we report the design, synthesis, antibacterial activities, and structure-activity relationships of a series of novel pleuromutilin derivatives containing a quaternary amine C-14 side chain. Most of these derivatives exhibited broad-spectrum antibacterial activity against the tested bacteria. 10b was the most effective antibacterial agent that displayed excellent antibacterial activity against five clinical methicillin-resistant Staphylococcus aureus (MRSA) isolates, remarkable antimycoplasma activity, rapid bactericidal effects, and a strong ability to damage bacterial biofilms. Further mechanistic studies indicated that 10b destroyed bacterial cell membranes to exert its antibacterial effects. Moreover, 10b exhibited high survival protection and potent in vivo antibacterial efficacy (ED50 = 4.94 mg/kg) in a mouse model of systemic MRSA infection. These findings suggest that 10b is a promising candidate for the treatment of multi-drug-resistant infectious diseases, especially MRSA infections.

[Research progress on chemical constituents, pharmacological activities and clinical application of Bolbostemma paniculatum].

Bolbostemma paniculatum is a commonly used Chinese medicinal material effective in clearing heat, removing toxin, eliminating phlegm, and alleviating swelling. The anti-tumor activity it possesses makes it a research hotspot. At present, 76 compounds have been isolated from B. paniculatum, including triterpenoids, sterols, alkaloids, anthraquinones, organic acids, etc., with anti-tumor, antiviral, and immunosuppressive pharmacological activities. This study reviewed the research on the chemical constituents and pharmacological effects of B. paniculatum over the past 20 years, aiming to provide a scientific basis for the research on the pharmacodynamic material basis and promote the development and utilization of B. paniculatum.