Next Article in Journal
Next Article in Special Issue
Previous Article in Journal
Previous Article in Special Issue
Molecules 2007, 12(10), 2380-2395; doi:10.3390/12102380
Article

Bioreversible Derivatives of Phenol. 1. The Role of Human Serum Albumin as Related to the Stability and Binding Properties of Carbonate Esters with Fatty Acid-like Structures in Aqueous Solution and Biological Media

*  and
Received: 28 September 2007; in revised form: 29 October 2007 / Accepted: 29 October 2007 / Published: 30 October 2007
(This article belongs to the collection Prodrugs)
Download PDF [118 KB, uploaded 18 June 2014]
Abstract: With the overall objective of assessing the potential of utilizing plasma protein binding interactions in combination with the prodrug approach for improving the pharmacokinetics of drug substances, a series of model carbonate ester prodrugs of phenol, encompassing derivatives with fatty acid-like structures, were characterized in vitro. Stability of the derivatives was studied in aqueous solution, human serum albumin solution, human plasma, and rat liver homogenate at 37°C. Stability of the derivatives in aqueous solution varied widely, with half-lives ranging from 31 to 1.7 × 104 min at pH 7.4 and 37°C. The carbonate esters were subject to catalysis by plasma esterases except for the t-butyl and acetic acid derivatives, which were stabilized in both human plasma and human serum albumin solutions relative to buffer. In most cases, however, hydrolysis was accelerated in the presence of human serum albumin indicating that the derivatives interacted with the protein, a finding which was confirmed using the p-nitrophenyl acetate kinetic assay. Different human serum albumin binding properties of the phenol model prodrugs with fatty acid-like structure and neutral carbonate esters were observed. In the context of utilizing plasma protein binding in combination with the prodrug approach for optimizing drug pharmacokinetics, the esterase-like properties of human serum albumin towards the carbonate esters potentially allowing the protein to act as a catalyst of parent compound regenerations is interesting.
Keywords: bioreversible derivatives; carbonate ester; esterase-like properties; human serum albumin; prodrug; plasma protein binding bioreversible derivatives; carbonate ester; esterase-like properties; human serum albumin; prodrug; plasma protein binding
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Export to BibTeX |
EndNote


MDPI and ACS Style

Ostergaard, J.; Larsen, C. Bioreversible Derivatives of Phenol. 1. The Role of Human Serum Albumin as Related to the Stability and Binding Properties of Carbonate Esters with Fatty Acid-like Structures in Aqueous Solution and Biological Media. Molecules 2007, 12, 2380-2395.

AMA Style

Ostergaard J, Larsen C. Bioreversible Derivatives of Phenol. 1. The Role of Human Serum Albumin as Related to the Stability and Binding Properties of Carbonate Esters with Fatty Acid-like Structures in Aqueous Solution and Biological Media. Molecules. 2007; 12(10):2380-2395.

Chicago/Turabian Style

Ostergaard, Jesper; Larsen, Claus. 2007. "Bioreversible Derivatives of Phenol. 1. The Role of Human Serum Albumin as Related to the Stability and Binding Properties of Carbonate Esters with Fatty Acid-like Structures in Aqueous Solution and Biological Media." Molecules 12, no. 10: 2380-2395.



Molecules EISSN 1420-3049 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert