Synthesis and analysis of ethylated tetracycline, an antibiotic derivative that inhibits the growth of tetracycline-resistant XL1-Blue bacteria.
Bacterial resistance to antibiotics is a significant problem in medical care facilities, causing increased fatalities due to infection. The present study demonstrates that antibiotic structures can be selectively altered in a manner that revives their ability to inhibit bacterial growth. The antibiotic tetracycline was ethylated at the position of the phenolic hydroxy group with the use of diazoethane, forming an ethyl ether functional group. This derivative was dissolved in Luria-Bertani (LB) agar medium, then placed in tissue culture for screening against a tetracycline-resistant bacterial strain. The growth of this bacterial strain, designated XL1-Blue, was inhibited by the ethylated form of tetracycline. The procedure for synthesizing ethylated tetracycline utilizes diazoethane and is presented with the molecular structures and IR spectra. The ethylated form of tetracycline was stable at -20 degrees C for many weeks, and was soluble in LB agar plate medium. Ethylated tetracycline induced growth inhibition of XL1-Blue bacteria within the first 24 h of incubation. The level of bacterial growth inhibition was greater than 30%. Calculation of the partition coefficient, log P, was accomplished and indicates that ethylated tetracycline has an increased lipophilic tendency relative to unmodified tetracycline, and therefore has greater solubility in lipid bilayers.
Bartzatt
R
R
Chemistry Department, College of Arts and Sciences, University of Nebraska, Omaha, NE 68182, USA. bartzatt@unomaha.edu
Koziol
K
K
Benish
T
T
Stoddard
J
J
D000085:Acetates; D000478:Alkylation; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis / Q000494:pharmacology*; D003979:Diazonium Compounds; D004926:Escherichia coli / Q000187:drug effects* / Q000254:growth & development*; D004986:Ether; D013752:Tetracycline / Q000138:chemical synthesis* / Q000494:pharmacology*; D013753:Tetracycline Resistance; D013754:Tetracyclines
D000085:Acetates; D000900:Anti-Bacterial Agents; D003979:Diazonium Compounds; D013754:Tetracyclines; D004986:Ether; C007650:ethyl acetate; D013752:Tetracycline