Synthesis and properties of disodium tetraethyleneglycol-bis-(alpha-carboxybenzylpenicillin).
Disodium tetraethyleneglycol-bis-(alpha-carboxybenzylpenicillin) (TEG-carbenicillin), a tetraethyleneglycol (TEG) diester of carbenicillin, was synthesized to develop a carbenicillin prodrug with enhanced acid stability for oral administration. Antimicrobial activities of TEG-carbenicillin tested against gram-negative Escherichia coli (TG-1) and gram-positive Staphylococcus aureus (ATCC-12228) and Bacillus subtilis (NA-1) were comparable to that of carbenicillin. Stability of the beta-lactam ring of TEG-carbenicillin was determined by iodometry at pH 6.8, pH 4.5, and pH 2.0 at varied time intervals and was compared to that of carbenicillin. In 26 hr, both of the compounds were stable at pH 6.8. At pH 4.5, about 41% of the carbenicillin was decomposed, while TEG-carbenicillin was not appreciably decomposed. At pH 2.0, carbenicillin was decomposed about 61% after 6 hr, while TEG-carbenicillin was decomposed about 21% during the same period.
Kim
Y T
YT
College of Pharmacy, Pusan National University, Korea.
Jung
Y J
YJ
Kim
Y M
YM
D000900:Anti-Bacterial Agents / Q000737:chemistry* / Q000494:pharmacology; D001412:Bacillus subtilis / Q000187:drug effects; D002228:Carbenicillin / Q000138:chemical synthesis* / Q000737:chemistry* / Q000494:pharmacology; D004355:Drug Stability; D004926:Escherichia coli / Q000187:drug effects; D006863:Hydrogen-Ion Concentration; D011355:Prodrugs / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D012995:Solubility; D013211:Staphylococcus aureus / Q000187:drug effects
D000900:Anti-Bacterial Agents; D011355:Prodrugs; D002228:Carbenicillin