Synthesis and analysis of ethylated tetracycline, an antibiotic derivativethat inhibits the growth of tetracycline-resistant XLI-Blue bacteria

Bacterial resistance to antibiotics is a significant problem in medical car e facilities, causing increased fatalities due to infection. The present st udy demonstrates that antibiotic structures can be selectively altered in a manner that revives their ability to inhibit bacterial growth. The antibio tic tetracycline was ethylated at the position of the phenolic hydroxy grou p with the use of diazoethane, forming an ethyl ether functional group, Thi s derivative was dissolved in Luria-Bertani (LB) agar medium, then placed i n tissue culture for screening against a tetracycline-resistant bacterial s train. The growth of this bacterial strain, designated XLI-Blue, was inhibi ted by the ethylated form of tetracycline. The procedure for synthesizing e thylated tetracycline utilizes diazoethane and is presented with the molecu lar structures and IR spectra, The ethylated form of tetracycline was stabl e at -20 degreesC for many weeks, and was soluble in LB agar plate medium, Ethylated tetracycline induced growth inhibition of XL I-Blue bacteria with in the first 24 h of incubation. The level of bacterial growth inhibition w as greater than 30%, Calculation of the partition coefficient, log P, was a ccomplished and indicates that ethylated tetracycline has an increased lipo philic tendency relative to unmodified tetracycline. and therefore has grea ter solubility in lipid bilayers.