Sci. Pharm. 2011; 79: 259–264
Chemical Stability of New Acyclovir Analogues with Peptidomimetics
Georgi HRISTOV, Ivanka STANKOVA *
Department of Chemistry, South-West University 'Neofit Rilski', Ivan Michailov str. 66, 2700 Blagoevgrad, Bulgaria.
* Corresponding author. E-mail: ivastankova@abv.bg (I. Stankova)
Abstract
In the search for new and effective prodrugs against the herpes simplex virus, a series of acyclovir analogues with a thiazole ring containing amino acids (glycine, alanine, valine, leucine) has been investigated. The chemical stability of some of the compounds containing different residues was studied at pH 1 and pH 7.4 at a temperature of 37°C. An HPLC method was developed for quantification of the unchanged ester concentration. Some of the esters (Gly-thiazole, Ala-thiazole-acyclovir, Leu-thiazole-acyclovir) were rather unstable, especially under acidic conditions, and underwent rapid hydrolysis into the chemical precursor acyclovir. At pH 7.4, the stability of Val-thiazole-acyclovir was remarkable. At this pH, Val-thiazole-acyclovir showed stability higher than that of valacyclovir (the first effective prodrug of acyclovir).
Keywords
Amino acids • Thiazole • Antiviral drugs • HPLC • Prodrugs
Received December 20th, 2010 | Accepted March 3rd, 2011 | Published Online March 5th, 2011
