Design, synthesis and biological evaluation of pleuromutilin-Schiff base hybrids as potent anti-MRSA agents in vitro and in vivo

Li, Bo; Zhang, Zhe; Zhang, Jianfeng; Liu, Jie; Zuo, Xiang-Yi; Chen, Fang; Zhang, Guangyu; Fang, Han-Qing; Jin, Zhen; Tang, You‐Zhi

doi:10.1016/j.ejmech.2021.113624

Cited by 27 publications

(16 citation statements)

References 29 publications

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“… 203 Pleuromutilin 364 isolated from Pleurotus mutilis fungus, showed activity against MRSA. 204 Osmundalactone 365, 5-hydroxy-hex-2-en-4-olide 366, spiromentins C 367, isolated from Tapinella atrotomentosa mushroom. These compounds proved to possess significant antibacterial activity against multi-resistant Acinetobacter baumannii and extended-spectrum β-lactamase (ESBL)-producing E. coli .…”

Section: Controlling Multi-resistant Pathogens Using Terrestrial/micr...mentioning

confidence: 99%

Antimicrobial potentials of natural products against multidrug resistance pathogens: a comprehensive review

et al. 2022

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Section: Controlling Multi-resistant Pathogens Using Terrestrial/micr...mentioning

confidence: 99%

Antimicrobial potentials of natural products against multidrug resistance pathogens: a comprehensive review

et al. 2022

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“…The bacteria used were MRSA (ATCC 43300) and three kinds S. aureus . The specific methods and conditionals were described in detail in our previous studies (Li et al, 2021; Zhang et al, 2020a).…”

Section: Methodsmentioning

confidence: 99%

“…As the first pleuromutilin drug used in human medicine, retapamulin ( 4 , Figure 1) has been approved by the U.S. Food and Drug Administration (FDA). Lefamulin ( 5 , Figure 1) was approved by the FDA to treat community‐acquired bacterial pneumonia in humans in 2019 (Li et al, 2021). The success of lefamulin attracted researchers to pay more attention to the development of pleuromutilin drugs.…”

Section: Introductionmentioning

confidence: 99%

Design, synthesis, antibacterial activity evaluation and molecular docking study of pleuromutilin derivatives bearing amide side chains

et al. 2022

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A seize of pleuromutilin derivatives containing amide side chains were designed and synthesized as potential antibiotics against Methicillin-resistant Staphylococcus aureus (MRSA). Among all target compounds (compounds 11-30), compound 25 was found to have the strongest antibacterial activity against MRSA (minimum inhibitory concentration = 0.5 μg/ml). The result of the timekill curves indicated that compound 25 could repress the growth of MRSA in vitro obviously (−3.72 log 10 CFU/ml reduction). Furthermore, molecular docking studies demonstrated that compound 25 was localized in the binding pocket of 50S ribosomal subunit (ΔGb = −8.99 kcal/mol). Besides, compound 25 displayed low cytotoxicity to RAW 264.7 cells. The results suggested that compound 25 might be further developed into a novel antimicrobial agent against MRSA.

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“…1 H NMR data and 13 C NMR data were acquired on a 400 Bruker NMR spectrometer or 600 Bruker NMR spectrometer Synthesis of Compound 2. 59 Compound 1 (15.14 g, 40 mmol), TsCl (9.15 g, 48 mmol), TEA (16.65 mL, 120 mmol), and DMAP (0.49 g, 4 mmol) were mixed with DCM (100 mL). The reaction mixture was stirred at room temperature for 6 h, and then the organic solvent was evaporated under reduced pressure.…”

Section: ■ Conclusionmentioning

confidence: 99%

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

Xia

Xin

et al. 2023

J. Med. Chem.

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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.

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Design, synthesis and biological evaluation of pleuromutilin-Schiff base hybrids as potent anti-MRSA agents in vitro and in vivo

Cited by 27 publications

References 29 publications

Antimicrobial potentials of natural products against multidrug resistance pathogens: a comprehensive review

Antimicrobial potentials of natural products against multidrug resistance pathogens: a comprehensive review

Design, synthesis, antibacterial activity evaluation and molecular docking study of pleuromutilin derivatives bearing amide side chains

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

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