%0 Journal Article
%T Design, synthesis, in vitro and in vivo evaluation and molecular docking study of novel pleuromutilin derivatives as antibacterial agents.
%A Liu J
%A Ren J
%A Zuo XY
%A Zhou KX
%A Tang YZ
%A Jin Z
%J Fitoterapia
%V 176
%N 0
%D 2024 Jul 29
%M 38821322
%F 3.204
%R 10.1016/j.fitote.2024.106046
%X 14 novel pleuromutilin derivatives were designed and synthesized as inhibitors against Staphylococcus aureus (S. aureus). The modification was focused on the C22 position of pleuromutilin. We conducted the characterization, in vitro and in vivo biological assessment of the compounds. Compound 18 exhibited the best antibacterial effect against MRSA (MIC = 0.015 μg/mL, MBC = 0.125 μg/mL). Compound 18 was further studied by time-kill kinetic and post-antibiotic effect (PAE) approaches. Besides, most compounds exhibited low cytotoxicity to RAW 264.7 cells. Compound 18 displayed decent bactericidal activity in vivo (-0.51 log10 CFU/mL). Molecular docking study indicated that compound 18 could be located stably at the ribosome (ΔGb = -7.30 kcal/mol). The results revealed that compound 18 might be further developed into a novel antibiotic.