Synthesis and analysis of a methyl ether derivative of tetracycline which inhibits growth of Escherichia coli.
Tetracycline is a widely used broad spectrum antibiotic. A derivative of tetracycline was synthesized by methylation (-CH3) of the phenolic hydroxyl group, with the use of diazomethane (CH2N2). A methyl ether group is then formed from the reaction with diazomethane, which replaces the hydroxyl group. The newly formed derivative has reduced hydrogen bonding capability relative to the unmodified tetracycline. An infrared spectra shows the appearance of the ether group on the derivative and the Log P calculations indicate that the derivative has increased lipophilic tendency. The Lipophilic Substituent Constant calculated for the tetracycline derivative is 0.46, indicating a lipophilic substituent. The tetracycline derivative was soluble in aqueous solvents and was stable for more than five weeks when stored at < or = 0 degrees C. The derivative was placed in tissue culture utilizing Luria-Bertani (LB) media, at a concentration of 12.0 microg/mL and inhibited the growth of E. coli (XL-1 blue) from 15% to 20% within the initial sixteen hours.
Bartzatt
Ronald
R
University of Nebraska, College of Arts and Sciences, Chemistry Department, Omaha 68182, USA.
Koziol
Kelly
K
Benish
Theresa
T
Stoddard
Jason
J
D000085:Acetates / Q000737:chemistry; D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000145:classification / Q000494:pharmacology; D002478:Cells, Cultured; D003978:Diazomethane / Q000737:chemistry; D004355:Drug Stability; D004926:Escherichia coli / Q000145:classification / Q000187:drug effects* / Q000254:growth & development*; D004986:Ether / Q000737:chemistry; D006131:Growth Inhibitors; D008745:Methylation; D012995:Solubility; D013045:Species Specificity; D013752:Tetracycline / Q000138:chemical synthesis / Q000737:chemistry* / Q000145:classification / Q000494:pharmacology*; D013753:Tetracycline Resistance
D000085:Acetates; D000900:Anti-Bacterial Agents; D006131:Growth Inhibitors; D004986:Ether; D003978:Diazomethane; C007650:ethyl acetate; D013752:Tetracycline