title: Prodrugs for masking bitter taste of antibacterial drugs--a computational approach.
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.
authors: Bioorganic Chemistry Department, Faculty of Pharmacy, Al-Quds University, Box 20002 Jerusalem, Palestine. dr_karaman@yahoo.com
authors: Rafik
authors: R
authors: Karaman
mesh_terms: D000900:Anti-Bacterial Agents / Q000737:chemistry*; D002444:Cefuroxime / Q000737:chemistry; D006868:Hydrolysis; D008958:Models, Molecular; D015394:Molecular Structure; D011355:Prodrugs / Q000737:chemistry*; D013649:Taste
chemical_list: D000900:Anti-Bacterial Agents; D011355:Prodrugs; D002444:Cefuroxime