Design, synthesis, and biological evaluation of novel pleuromutilin derivatives containing benzimidazoles as effective anti‐MRSA agents

Abstract

A series of pleuromutilin derivatives containing benzimidazole were designed, synthesized, and evaluated for their antibacterial activities against Methicillin‐resistant Staphylococcus aureus (MRSA) in this study. The in vitro antibacterial activities of the synthesized derivatives against four strains of S. aureus (MRSA ATCC 43300, S. aureus ATCC 29213, S. aureus 144, and S. aureus AD3) were determined by the broth dilution method. Among these derivatives, compound 58 exhibited superior in vitro antibacterial effect against MRSA (minimal inhibitory concentration [MIC] = 0.0625 μg/mL) than tiamulin (MIC = 0.5 μg/mL). Compound 58 possessed a faster bactericidal kinetic and a longer post‐antibiotic effect time against MRSA than tiamulin. Meanwhile, at 8 μg/mL concentration, compound 58 did not display obviously cytotoxic effect on the RAW 264.7 cells. In addition, compound 58 (−2.04 log10 CFU/mL) displayed superior in vivo antibacterial efficacy than tiamulin (−1.02 log10 CFU/mL) in reducing MRSA load in mice thigh infection model. In molecular docking study, compound 58 can successfully attach to the 50S ribosomal active site (the binding free energy is −8.11 kcal/mol). Therefore, compound 58 was a potential antibacterial candidate for combating MRSA infections.

Three Polyoxometalate-Based Ag–Organic Compounds as Heterogeneous Catalysts for the Synthesis of Benzimidazoles

“…Heterocyclic compounds play an essential role in the development of contemporary materials science, the pharmaceutical industry, synthetic organic chemistry, and so on. , For example, benzimidazoles and their derivatives emerged as a very important class of N-heterocyclic systems due to their remarkable biological characteristics of anticonvulsant, anti-inflammatory, antiallergic, antipyretic, antidepressive, and others. − It has been also found in several common drugs, such as omeprazole, maribavir, bendamustine, nocodazole, Albendazole, Mebendazole, and so on. − In this sense, the synthesis of benzimidazole is quite important for the current time attributing its increasing applications to the development medicinal field. − However, the synthesis of benzimidazole has faced some problems, such as low yields, more byproducts, harsh reaction conditions, and so on. ,,− Therefore, it is still necessary to develop catalytic systems for the construction of benzimidazole with the advantages of simple operation, catalyst recyclability, and high yield.…”