A click chemistry approach to pleuromutilin derivatives. Part 3: extended footprinting analysis and excellent MRSA inhibition for a derivative with an adenine phenyl side chain.
Five promising pleuromutilin derivatives from our former studies, all containing adenine on various linkers, were supplemented with two new compounds. The binding to Escherichia coli ribosomes was verified by extensive chemical footprinting analysis. The ability to inhibit bacterial growth was investigated on two Staphylococcus aureus strains and compared to the pleuromutilin drugs tiamulin and valnemulin. Three of the compounds show an effect similar to tiamulin and one compound shows an excellent effect similar to valnemulin.
Nucleic Acid Center, Department of Physics, Chemistry and Pharmacy, University of Southern Denmark, 5230 Odense M, Denmark.
Ida
I
Dreier
Nucleic Acid Center, Department of Biochemistry and Molecular Biology, University of Southern Denmark, 5230 Odense M, Denmark.
Lykke H
LH
Hansen
Nucleic Acid Center, Department of Physics, Chemistry and Pharmacy, University of Southern Denmark, 5230 Odense M, Denmark. Electronic address: pouln@sdu.dk.
Poul
P
Nielsen
Nucleic Acid Center, Department of Biochemistry and Molecular Biology, University of Southern Denmark, 5230 Odense M, Denmark. Electronic address: b.vester@bmb.sdu.dk.
Birte
B
Vester
D000225:Adenine / Q000031:analogs & derivatives / Q000737:chemistry*; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D057930:Click Chemistry; D004224:Diterpenes / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D055624:Methicillin-Resistant Staphylococcus aureus / Q000187:drug effects* / Q000254:growth & development; D008826:Microbial Sensitivity Tests; D008968:Molecular Conformation; D011083:Polycyclic Compounds; D013329:Structure-Activity Relationship; D000097567:Pleuromutilins
D000225:Adenine; D000900:Anti-Bacterial Agents; D004224:Diterpenes; D011083:Polycyclic Compounds; D000097567:Pleuromutilins
Antibiotics; Chemical footprinting; Click chemistry; MRSA inhibition; Pleuromutilin derivatives