Design, synthesis, and structure–activity relationship studies of novel pleuromutilin derivatives having a piperazine ring

Abstract

A series of novel pleuromutilin derivatives possessing piperazine moieties were synthesized under mild conditions. The in vitro antibacterial activities of these derivatives against Staphylococcus aureus and Escherichia coli were tested by the agar dilution method. Structure-activity relationship studies resulted in compounds 11b, 13b, and 14a with the most potent in vitro antibacterial activity among the series (minimal inhibitory concentration = 0.0625-0.125 μg/mL). The binding of compounds 11b, 13b, and 14a to the E. coli ribosome was investigated by molecular modeling, and it was found that there is a reasonable correlation between the binding free energy and the antibacterial activity.

Synthesis, biological activities and docking studies of pleuromutilin derivatives with piperazinyl urea linkage

“…Compound 8 was collected after silica gel column chromatography (Yield: 75.2%). Spectral data results of 8 were identical to those from reports in the literature 28 .…”

Piperazine skeleton in the structural modification of natural products: a review

“…The compound-bearing nitro group in the para-position showed higher activity compared to other para-position substituted derivatives. The para-position appeared to have less influence on the antibacterial activity of these pleuromutilin derivatives bearing a phenyl piperazine 110 . In 2015, derivative 83 (Figure 46) was revealed remarkable activity against S. aureus (ATCC25923; MIC of 0.125 mg/mL), which is equal to the control compound tiamulin.…”

Synthesis and antibacterial activities of novel pleuromutilin derivatives

“…Analogues 4a–h were obtained from the reaction of iodide group of compound 3 and the secondary amines. Compound 4h has been reported by Luo and coworkers . Here we synthesized these compounds again for the supplements to compounds 4a–g and compared their antibacterial activities.…”