title: Synthesis and evaluation of novel pleuromutilin derivatives with a substituted pyrimidine moiety.
abstract: A series of novel pleuromutilin derivatives possessing 6-hydroxy pyrimidine moieties were synthesized via acylation reactions under mild conditions. The in vitro antibacterial activities of the synthesized derivatives against methicillin-resistant Staphylococcus aureus (MRSA), methicillin-resistant Staphylococcus epidermidis (MRSE), Bacillus subtilis (B. subtilis), and Escherichia coli (E. coli) were tested by the agar dilution method. The majority of the screened compounds displayed potent activities. Compounds 3 and 6a were found to be the most active antibacterial agents against MRSA and MRSE. Moreover, in the vivo experiment, compound 6a showed comparable antibacterial activity to that of tiamulin, with ED50 of 5.47 mg/kg body weight against MRSA.
authors.affiliation: Key Laboratory of New Animal Drug Project of Gansu Province, Key Laboratory of Veterinary Pharmaceutical Development, Ministry of Agriculture, Lanzhou Institute of Husbandry and Pharmaceutical Sciences of CAAS, Lanzhou 730050, China. Electronic address: yiyp2013@163.com.
authors.forename: Yunpeng
authors.initials: Y
authors.lastname: Yi
authors.affiliation: School of Pharmacy, Lanzhou University, 199 West Donggang Road, Lanzhou, 730020, China.
authors.forename: Guanzhou
authors.initials: G
authors.lastname: Yang
authors.affiliation: Key Laboratory of New Animal Drug Project of Gansu Province, Key Laboratory of Veterinary Pharmaceutical Development, Ministry of Agriculture, Lanzhou Institute of Husbandry and Pharmaceutical Sciences of CAAS, Lanzhou 730050, China.
authors.forename: Chao
authors.initials: C
authors.lastname: Zhang
authors.affiliation: Key Laboratory of New Animal Drug Project of Gansu Province, Key Laboratory of Veterinary Pharmaceutical Development, Ministry of Agriculture, Lanzhou Institute of Husbandry and Pharmaceutical Sciences of CAAS, Lanzhou 730050, China.
authors.forename: Jiongran
authors.initials: J
authors.lastname: Chen
authors.affiliation: Key Laboratory of New Animal Drug Project of Gansu Province, Key Laboratory of Veterinary Pharmaceutical Development, Ministry of Agriculture, Lanzhou Institute of Husbandry and Pharmaceutical Sciences of CAAS, Lanzhou 730050, China.
authors.forename: Jianping
authors.initials: J
authors.lastname: Liang
authors.affiliation: Key Laboratory of New Animal Drug Project of Gansu Province, Key Laboratory of Veterinary Pharmaceutical Development, Ministry of Agriculture, Lanzhou Institute of Husbandry and Pharmaceutical Sciences of CAAS, Lanzhou 730050, China. Electronic address: shangrf1974@163.com.
authors.forename: Ruofeng
authors.initials: R
authors.lastname: Shang
mesh_terms: D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D001412:Bacillus subtilis / Q000187:drug effects*; D004224:Diterpenes / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004926:Escherichia coli / Q000187:drug effects*; D016106:Methicillin Resistance / Q000187:drug effects; D008826:Microbial Sensitivity Tests; D008958:Models, Molecular; D008968:Molecular Conformation; D011083:Polycyclic Compounds; D011743:Pyrimidines / Q000737:chemistry*; D013211:Staphylococcus aureus / Q000187:drug effects*; D013329:Structure-Activity Relationship; D000097567:Pleuromutilins
chemical_list: D000900:Anti-Bacterial Agents; D004224:Diterpenes; D011083:Polycyclic Compounds; D011743:Pyrimidines; D000097567:Pleuromutilins; C030986:pyrimidine
keywords: Antibacterial activity; MRSA; Pleuromutilin derivatives; Synthesis