722539-52-8Relevant academic research and scientific papers
Second Generation of cycloSal-Pronucleotides with Esterase-Cleavable Sites: The "Lock-In"-Concept
Meier, Chris,Ruppel, Manuel F. H.,Vukadinovic, Dalibor,Balzarini, Jan
, p. 89 - 115 (2004)
A conceptual extension of the cycloSal-pronucleotide approach is presented. The characteristic feature of the new cycloSal-derivatives of the anti-HIV active nucleoside analogue d4T 1 is the incorporation of an enzymatically cleavable carboxylic ester moiety with the intention to trap the triesters inside cells ("lock-in"-concept). CycloSal-triesters bearing different ester groups in the 3-or 5-position of the cycloSal-moiety are described. Surprisingly, only acetyl-and levulinyl esters are cleaved readily in CEM cell extracts while alkyl esters were found to be stable. Nevertheless, in in-vitro anti-HIV assays most of the compounds achieve the thymidine-kinase bypass, thus proving that they act at least as nucleotide delivery systems.
Second-generation cycloSal-d4TMP pronucleotides bearing esterase-cleavable sites - The "trapping" concept
Meier, Chris,Ducho, Christian,Jessen, Henning,Vukadinovic-Tenter, Dalibor,Balzarini, Jan
, p. 197 - 206 (2007/10/03)
An extension of the cycloSal-pronucleotide approach is presented. Attachment of an enzyme-cleavable ester/acylal group to the cycloSal-d4TMP triesters should allow these compounds to be trapped intracellularly after cleavage. The ester/acylal groups were introduced in the 3- or 5-position of the cycloSal ring system, and surprising differences were observed in hydrolysis studies in CEM cell extracts with respect to the ester/acylal moiety. While acetyl and levulinyl esters were readily cleaved, alkyl esters of cycloSal-d4TMP acids proved to be resistant to enzymatic cleavage. In contrast, AM-, POM- and POC-acylals were rapidly cleaved in the extracts, leading to cycloSal-d4TMP acids. The antiviral activity of the compounds against HIV is also presented. Wiley-VCH Verlag GmbH & Co. KGaA, 2006.
