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Article

Discovery of Novel Pleuromutilin Derivatives as Potent Antibacterial Agents for the Treatment of MRSA Infection

1
Guangdong Provincial Key Laboratory of Veterinary Pharmaceutics Development and Safety Evaluation, College of Veterinary Medicine, South China Agricultural University, No. 483 Wushan Road, Tianhe District, Guangzhou 510642, China
2
Guangdong Laboratory for Lingnan Modern Agriculture, Guangzhou 510642, China
*
Author to whom correspondence should be addressed.
Academic Editor: Michio Kurosu
Molecules 2022, 27(3), 931; https://doi.org/10.3390/molecules27030931
Received: 29 December 2021 / Revised: 22 January 2022 / Accepted: 26 January 2022 / Published: 29 January 2022
(This article belongs to the Special Issue Antibacterial Agents 2021)
A series of novel pleuromutilin derivatives containing nitrogen groups on the side chain of C14 were synthesized under mild conditions. Most of the synthesized derivatives displayed potent antibacterial activities. Compound 9 was found to be the most active antibacterial derivative against MRSA (MIC = 0.06 μg/mL). Furthermore, the result of time-kill curves showed that compound 9 had a certain inhibitory effect against MRSA in vitro. Moreover, according to a surface plasmon resonance (SPR) study, compound 9 (KD = 1.77 × 10−8 M) showed stronger affinity to the 50S ribosome than tiamulin (KD = 2.50 × 10−8 M). The antibacterial activity of compound 9 was further evaluated in an MRSA-infected murine thigh model. Compared to the negative control group, tiamulin reduced MRSA load (~0.7 log10 CFU/mL), and compound 9 performed a treatment effect (~1.3 log10 CFU/mL). In addition, compound 9 was evaluated in CYP450 inhibition assay and showed only moderate in vitro CYP3A4 inhibition (IC50 = 2.92 μg/mL). View Full-Text
Keywords: antibacterial activity; MRSA; pleuromutilin; SPR; 50S ribosome antibacterial activity; MRSA; pleuromutilin; SPR; 50S ribosome
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MDPI and ACS Style

Fang, H.-Q.; Zeng, J.; Wang, S.-K.; Wang, X.; Chen, F.; Li, B.; Liu, J.; Jin, Z.; Liu, Y.-H.; Tang, Y.-Z. Discovery of Novel Pleuromutilin Derivatives as Potent Antibacterial Agents for the Treatment of MRSA Infection. Molecules 2022, 27, 931. https://doi.org/10.3390/molecules27030931

AMA Style

Fang H-Q, Zeng J, Wang S-K, Wang X, Chen F, Li B, Liu J, Jin Z, Liu Y-H, Tang Y-Z. Discovery of Novel Pleuromutilin Derivatives as Potent Antibacterial Agents for the Treatment of MRSA Infection. Molecules. 2022; 27(3):931. https://doi.org/10.3390/molecules27030931

Chicago/Turabian Style

Fang, Han-Qing, Jie Zeng, Shou-Kai Wang, Xiao Wang, Fang Chen, Bo Li, Jie Liu, Zhen Jin, Ya-Hong Liu, and You-Zhi Tang. 2022. "Discovery of Novel Pleuromutilin Derivatives as Potent Antibacterial Agents for the Treatment of MRSA Infection" Molecules 27, no. 3: 931. https://doi.org/10.3390/molecules27030931

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