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Analysis of an ampicillin propyl ester prodrug which inhibits the growth of Escherichia coli
Author(s) -
Bartzatt Ronald,
Malesa Cynthia
Publication year - 2002
Publication title -
biotechnology and applied biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.468
H-Index - 70
eISSN - 1470-8744
pISSN - 0885-4513
DOI - 10.1042/ba20020003
Subject(s) - prodrug , ampicillin , chemistry , substituent , escherichia coli , partition coefficient , chromatography , organic chemistry , biochemistry , antibiotics , gene
An ampicillin prodrug was synthesized by utilizing the chemical reaction of ampicillin with diazopropane (CH 3 CH 2 CHN 2 ) in an organic solvent. The result is esterification of the carboxylic acid functional group. The ampicillin prodrug is a solid that forms yellow crystals which are soluble in water and LB agarose media. The ampicillin prodrug was stable for more than 10 weeks when stored at 0.0 °C. The prodrug has reduced hydrogen‐bonding capability compared with the unmodified structure of ampicillin. Evaluation of the logP parameter (the octanol/water partition coefficient) indicates that the ampicillin prodrug (logP=1.773) has increased lipophilic characteristics relative to the unmodified ampicillin structure (logP=1.06). The lipophilic substituent constant for the esterification of the carboxylic acid is 0.713, a positive value which indicates that the substituent has a lipophilic nature. The ampicillin prodrug was solubilized into LB agarose media at a concentration of 0.228 mg/ml, and was found to induce 100% growth inhibition of an ampicillin‐susceptible and streptomycin‐resistant Escherichia coli strain (designated DH1), and induced greater than 30% growth inhibition of an ampicillin‐resistant E. coli strain (designated PKK). Synthesis of this prodrug utilizing a diazoalkane was highly efficient, with no undesirable by‐products being formed.