Synthesis and antimicrobial activity of amide derivatives of polyether antibiotic-salinomycin.
For the first time a direct and practical approach to the synthesis of eight amide derivatives of polyether antibiotic-salinomycin is described. The structure of allyl amide (3a) has been determined using X-ray diffraction. Salinomycin and its amide derivatives have been screened for their in vitro antimicrobial activity against the typical gram-positive cocci, gram-negative rods and yeast-like organisms, as well as against a series of clinical isolates of methicillin-resistant Staphylococcus aureus and methicillin-sensitive S. aureus. Amides of salinomycin have been found to show a wide range of activities, from inactive at 256 μg/mL to active with MIC of 2 μg/mL, comparable with salinomycin. As a result, phenyl amide (3b) was found to be the most active salinomycin derivative against gram-positive bacteria, MRSA and MSSA.
Faculty of Chemistry, A. Mickiewicz University, Grunwaldzka 6, 60-780 Poznań, Poland. adhucz@amu.edu.pl
Adam
A
Huczyński
Jan
J
Janczak
Joanna
J
Stefańska
Michał
M
Antoszczak
Bogumil
B
Brzezinski
D000577:Amides / Q000737:chemistry*; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D004986:Ether / Q000737:chemistry*; D006860:Hydrogen Bonding; D008958:Models, Molecular; D015394:Molecular Structure; D011714:Pyrans / Q000737:chemistry* / Q000494:pharmacology; D013211:Staphylococcus aureus / Q000187:drug effects; D013329:Structure-Activity Relationship; D000095662:Polyether Polyketides
D000577:Amides; D000900:Anti-Bacterial Agents; D004986:Ether; D011714:Pyrans; C010327:salinomycin; D000095662:Polyether Polyketides