Year: 2026
Type: article
Abstract: ABSTRACT A novel pleuromutilin derivative, compound 4g with a cyclobutyl side chain, was identified and found to have good antibacterial activity, including methicillin‐resistant Staphylococcus aureus (MRSA) and Mycoplasma . In order to evaluate its safety profile, acute and 28‐day oral toxicity studies were carried out. An acute toxicity study in rats revealed that the oral LD 50 of 4g exceeded 5000 mg/kg, indicating that the compound had low acute toxicity. In a 28‐day oral toxicity test, the rats were repeatedly administered 0, 300, 1000, and 3000 mg/kg doses and showed no adverse clinical symptoms or death. Although 4g did not affect body weight, hematological findings indicated dose‐dependent inflammatory changes at 1000 and 3000 mg/kg. Serum biochemistry showed decreases in alanine aminotransferase (ALT) and alkaline phosphatase (ALP), suggesting adaptive metabolic responses rather than classic hepatocellular injury. Significantly, dose‐dependent increases in relative liver weight were observed at all dose levels, accompanied by minimal hepatocyte steatosis and altered serum lipid profiles, identifying the liver as a primary target organ. Based on the totality of findings, the no‐observed‐adverse‐effect level (NOAEL) was determined to be 300 mg/kg. In conclusion, pleuromutilin derivative 4g has low toxicity, which provides the theoretical basis to further investigate for a new candidate drug.
Source: Journal of Applied Toxicology
DOI: 10.1002/jat.70104
Authors: He‐Chao Zhang, Zhun Li, Zhe Qin, Wen‐Bo Ge, Ya‐Jun Yang, Jian‐Yong Li
Language: English
Subfield: Immunology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: green
Award: G45683792
OpenAlex ID: W7128958627