Prodrugs for Masking Bitter Taste of Antibacterial Drugs - A Computational Approach

Date
2013-02-19
Authors
Karaman, Rafik
Journal Title
Journal ISSN
Volume Title
Publisher
Springer-Verlag
Abstract
DFT calculations for the acid-catalyzed hydrolysis of several maleamic acid amide derivatives revealed that the reaction rate-limiting step is determined on the nature of the amine leaving group. Further, it was established that when the amine leaving group was a secondary amine, acyclovir or cefuroxime moiety the tetrahedral intermediate formation was the rate-limiting step such as in the cases of acyclovir ProD 1- ProD 4 and cefuroxime ProD 1- ProD 4. In addition, the linear correlation between the calculated and experimental rates provided a credible basis for designing prodrugs for masking bitter taste of the corresponding parental drugs which have the potential to release the parent drug in a sustained release fashion. For example, based on the DFT calculated rates the predicted t1/2 (a time needed for 50 % of the reactant to be hydrolyzed to products) for cefuroxime prodrugs, cefuroxime ProD 1- ProD 4, were 12 min, 18 min, 200 min and 123 min, respectively.
Description
Keywords
Antibacterial prodrugs, Cefuroxime prodrugs, DFTcalculations, Intramolecular amide hydrolysis, Maleamic acid amides, Masking bitter taste
Citation