Novel pleuromutilin derivatives with substituted 6-methylpyrimidine: Design, synthesis and antibacterial evaluation. 2020

Yuan Fan, and Yu Liu, and Hao Wang, and Tao Shi, and Feng Cheng, and Baocheng Hao, and Yunpeng Yi, and Ruofeng Shang
Key Laboratory of New Animal Drug Project, Gansu Province, China; Key Laboratory of Veterinary Pharmaceutical Development, Ministry of Agriculture and Rural Affairs, China; Lanzhou Institute of Husbandry and Pharmaceutical Sciences of CAAS, No. 335, Qilihe District, Lanzhou, 730050, China. Electronic address: fanyuan666@163.com.

A series of novel pleuromutilin derivatives with substituted 6-methylpyrimidine moieties was designed, synthesized, and evaluated for their antibacterial activities. Most of the tested compounds exhibited potent antibacterial activities against Staphylococcus aureus ATCC 25923 (S. aureus-25923), methicillin-resistant Staphylococcus epidermidis ATCC 51625 (MRSE-51625), methicillin-resistant Staphylococcus aureus BNCC 337371 (MRSA-337371), Streptococcus dysgalactiae (S. dysgalactiae) and Streptococcus agalactiae (S. agalactiae). Compounds 5c and 5g were the most active and displayed bacteriostatic activities against MRSA. In vivo mouse systemic infection experiment showed that 5c significantly improved the survival rate of mice (ED50 = 18.02 mg/kg), reduced the bacterial load and alleviated the pathological changes in the lungs of the affected mice.

UI MeSH Term Description Entries
D008958 Models, Molecular Models used experimentally or theoretically to study molecular shape, electronic properties, or interactions; includes analogous molecules, computer-generated graphics, and mechanical structures. Molecular Models,Model, Molecular,Molecular Model
D011083 Polycyclic Compounds Compounds which contain two or more rings in their structure. Compounds, Polycyclic
D011743 Pyrimidines A family of 6-membered heterocyclic compounds occurring in nature in a wide variety of forms. They include several nucleic acid constituents (CYTOSINE; THYMINE; and URACIL) and form the basic structure of the barbiturates.
D004224 Diterpenes Twenty-carbon compounds derived from MEVALONIC ACID or deoxyxylulose phosphate. Diterpene,Diterpenes, Cembrane,Diterpenes, Labdane,Diterpenoid,Labdane Diterpene,Norditerpene,Norditerpenes,Norditerpenoid,Cembranes,Diterpenoids,Labdanes,Norditerpenoids,Cembrane Diterpenes,Diterpene, Labdane,Labdane Diterpenes
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000097567 Pleuromutilins A tricyclic diterpene natural product isolated from Pleurotus mutilus (now referred to as Clitopilus scyphoides). Possesses modest antibacterial activity against primarily gram-positive bacterial organisms. Octahydro-5,8-dihydroxy-4,6,9,10- tetramethyl-6-vinyl-3a,9-propano-3aH-cyclopenta- cycloocten-1(4H)-one 8-glycolate,Pleuromutilin,Pleuromutilin Antibiotics,Drosophilin B
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D000900 Anti-Bacterial Agents Substances that inhibit the growth or reproduction of BACTERIA. Anti-Bacterial Agent,Anti-Bacterial Compound,Anti-Mycobacterial Agent,Antibacterial Agent,Antibiotics,Antimycobacterial Agent,Bacteriocidal Agent,Bacteriocide,Anti-Bacterial Compounds,Anti-Mycobacterial Agents,Antibacterial Agents,Antibiotic,Antimycobacterial Agents,Bacteriocidal Agents,Bacteriocides,Agent, Anti-Bacterial,Agent, Anti-Mycobacterial,Agent, Antibacterial,Agent, Antimycobacterial,Agent, Bacteriocidal,Agents, Anti-Bacterial,Agents, Anti-Mycobacterial,Agents, Antibacterial,Agents, Antimycobacterial,Agents, Bacteriocidal,Anti Bacterial Agent,Anti Bacterial Agents,Anti Bacterial Compound,Anti Bacterial Compounds,Anti Mycobacterial Agent,Anti Mycobacterial Agents,Compound, Anti-Bacterial,Compounds, Anti-Bacterial
D013203 Staphylococcal Infections Infections with bacteria of the genus STAPHYLOCOCCUS. Infections, Staphylococcal,Staphylococcus aureus Infection,Staphylococcal Infection,Staphylococcus aureus Infections
D013210 Staphylococcus A genus of gram-positive, facultatively anaerobic, coccoid bacteria. Its organisms occur singly, in pairs, and in tetrads and characteristically divide in more than one plane to form irregular clusters. Natural populations of Staphylococcus are found on the skin and mucous membranes of warm-blooded animals. Some species are opportunistic pathogens of humans and animals.

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