{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,25]],"date-time":"2025-11-25T06:59:14Z","timestamp":1764053954425,"version":"build-2065373602"},"reference-count":39,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2025,5,29]],"date-time":"2025-05-29T00:00:00Z","timestamp":1748476800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Inner Mongolia Autonomous Region \u201cUniversity Youth Science and Technology talents\u201d","award":["NJYT22041","2022MS03048","2023LHMS03015","BR220111","YLXKZX-NND-012","2020GG0042","YKD2022QN036"],"award-info":[{"award-number":["NJYT22041","2022MS03048","2023LHMS03015","BR220111","YLXKZX-NND-012","2020GG0042","YKD2022QN036"]}]},{"name":"Inner Mongolia Natural Science Foundation project","award":["NJYT22041","2022MS03048","2023LHMS03015","BR220111","YLXKZX-NND-012","2020GG0042","YKD2022QN036"],"award-info":[{"award-number":["NJYT22041","2022MS03048","2023LHMS03015","BR220111","YLXKZX-NND-012","2020GG0042","YKD2022QN036"]}]},{"name":"Inner Mongolia Agricultural University young teachers research ability promotion project","award":["NJYT22041","2022MS03048","2023LHMS03015","BR220111","YLXKZX-NND-012","2020GG0042","YKD2022QN036"],"award-info":[{"award-number":["NJYT22041","2022MS03048","2023LHMS03015","BR220111","YLXKZX-NND-012","2020GG0042","YKD2022QN036"]}]},{"name":"Inner Mongolia Autonomous Region First Class Discipline Research Special Project","award":["NJYT22041","2022MS03048","2023LHMS03015","BR220111","YLXKZX-NND-012","2020GG0042","YKD2022QN036"],"award-info":[{"award-number":["NJYT22041","2022MS03048","2023LHMS03015","BR220111","YLXKZX-NND-012","2020GG0042","YKD2022QN036"]}]},{"name":"Science and Technology Program of the Inner Mongolia Autonomous Region","award":["NJYT22041","2022MS03048","2023LHMS03015","BR220111","YLXKZX-NND-012","2020GG0042","YKD2022QN036"],"award-info":[{"award-number":["NJYT22041","2022MS03048","2023LHMS03015","BR220111","YLXKZX-NND-012","2020GG0042","YKD2022QN036"]}]},{"name":"Inner Mongolia Medical University Youth Project","award":["NJYT22041","2022MS03048","2023LHMS03015","BR220111","YLXKZX-NND-012","2020GG0042","YKD2022QN036"],"award-info":[{"award-number":["NJYT22041","2022MS03048","2023LHMS03015","BR220111","YLXKZX-NND-012","2020GG0042","YKD2022QN036"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>The pleuromutilin derivative, the compound PL-W, was synthesized by introducing a 4-fluorophenyl group at the C21 position and selected for comprehensive antibacterial evaluation. PL-W demonstrated notable antibacterial activity against methicillin-resistant Staphylococcus aureus (MRSA), with a minimum inhibitory concentration (MIC) of 0.03125 \u00b5g\/mL, which is significantly lower than that of tiamulin (0.5 \u00b5g\/mL). Crystal violet (CV) staining revealed that it inhibited MRSA biofilm formation and electron microscopy revealed that it disrupted bacterial cell division and, possibly, the synthesis of essential cell wall proteins. In both in vivo models, PL-W exhibited excellent performance. In the Galleria mellonella infection model, treatment with different concentrations of PL-W increased the survival rate from 20% to 90% and significantly reduced the bacterial load. In the mouse model of MRSA pneumonia, a 10 mg\/kg dose of PL-W increased the survival rate to 70%, decreased the bacterial load in the lungs, and alleviated inflammatory damage. Molecular docking studies indicated that PL-W had a similar docking pose and comparable binding affinity to that of lefamulin, with hydrogen bond interactions that are crucial for binding to the peptidyl transferase center (PTC). Moreover, it demonstrated no significant reduction in cell viability in HepG2 and HEK293 cells, even at high concentrations (\u226450 \u00b5g\/mL). Overall, PL-W shows significant potential as a novel anti-MRSA agent owing to its potent in vitro and in vivo activities and low cytotoxicity.<\/jats:p>","DOI":"10.3390\/molecules30112366","type":"journal-article","created":{"date-parts":[[2025,5,29]],"date-time":"2025-05-29T06:25:04Z","timestamp":1748499904000},"page":"2366","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["The Synthesis and Biological Evaluation of a Novel Pleuromutilin Derivative Containing a 4-Fluorophenyl Group Targeting MRSA"],"prefix":"10.3390","volume":"30","author":[{"given":"Yongfei","family":"Wang","sequence":"first","affiliation":[{"name":"Laboratory of Veterinary Clinical Pharmacology, College of Veterinary Medicine, Inner Mongolia Agricultural University, No. 29, Erdosdong Road, Hohhot 010011, China"},{"name":"Experimental Animal Center, Inner Mongolia Medical University, Hohhot 010110, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-2950-230X","authenticated-orcid":false,"given":"Yi","family":"Zhao","sequence":"additional","affiliation":[{"name":"Laboratory of Veterinary Clinical Pharmacology, College of Veterinary Medicine, Inner Mongolia Agricultural University, No. 29, Erdosdong Road, Hohhot 010011, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Haiting","family":"Wang","sequence":"additional","affiliation":[{"name":"Shandong Provincial Animal and Poultry Green Health Products Creation Engineering Laboratory, Institute of Poultry Science, Shandong Academy of Agricultural Science, Jinan 250100, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bo","family":"Liu","sequence":"additional","affiliation":[{"name":"Laboratory of Veterinary Clinical Pharmacology, College of Veterinary Medicine, Inner Mongolia Agricultural University, No. 29, Erdosdong Road, Hohhot 010011, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shuangyi","family":"Zhang","sequence":"additional","affiliation":[{"name":"Laboratory of Veterinary Clinical Pharmacology, College of Veterinary Medicine, Inner Mongolia Agricultural University, No. 29, Erdosdong Road, Hohhot 010011, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuan","family":"Liu","sequence":"additional","affiliation":[{"name":"Laboratory of Veterinary Clinical Pharmacology, College of Veterinary Medicine, Inner Mongolia Agricultural University, No. 29, Erdosdong Road, Hohhot 010011, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ruinan","family":"Li","sequence":"additional","affiliation":[{"name":"Laboratory of Veterinary Clinical Pharmacology, College of Veterinary Medicine, Inner Mongolia Agricultural University, No. 29, Erdosdong Road, Hohhot 010011, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tao","family":"Zhang","sequence":"additional","affiliation":[{"name":"Laboratory of Veterinary Clinical Pharmacology, College of Veterinary Medicine, Inner Mongolia Agricultural University, No. 29, Erdosdong Road, Hohhot 010011, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Surong","family":"Hasi","sequence":"additional","affiliation":[{"name":"Laboratory of Veterinary Clinical Pharmacology, College of Veterinary Medicine, Inner Mongolia Agricultural University, No. 29, Erdosdong Road, Hohhot 010011, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wei","family":"Mao","sequence":"additional","affiliation":[{"name":"Laboratory of Veterinary Clinical Pharmacology, College of Veterinary Medicine, Inner Mongolia Agricultural University, No. 29, Erdosdong Road, Hohhot 010011, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,5,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"837","DOI":"10.1016\/j.chom.2024.05.015","article-title":"Antibiotic resistance: A key microbial survival mechanism that threatens public health","volume":"32","author":"Abbas","year":"2024","journal-title":"Cell Host Microbe"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Terreni, M., Taccani, M., and Pregnolato, M. 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