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