Synthesis and quantitative structure-activity relationship of hydrazones of N-amino-N′-hydroxyguanidine as electron acceptors for xanthine oxidase

Peteris Prusis, Maija Dambrova, Victor Andrianov, Eugene Rozhkov, Valentina Semenikhina, Irena Piskunova, Enock Ongwae, Torbjörn Lundstedt, Ivars Kalvinsh, Jarl E.S. Wikberg

Research output: Contribution to journalArticlepeer-review

26 Citations (Scopus)

Abstract

A series of new N-hydroxyguanidines were synthesized and tested for electron acceptor activity on bovine milk xanthine oxidase using xanthine as reducing substrate. Manual inspection of the structure-activity data revealed that molecules containing nitro groups ("set A") show a different structure-activity relationship pattern compared to non-nitro compounds ("set B"). Accordingly separate QSAR models were built and validated for the two sets. Substantial differences were found in properties governing acceptor activity for the models, the only common property being sterical access to the imino nitrogen atom of the hydroxyguanidinimines. For set A molecules the presence of a nitro substituent at a certain distance range from the hydroxuguanidino group was most important. In addition, the presence of a nitro group in the ortho position interacting with NH2 of the hydroxyguanidino group, and the mutual geometry of the phenyl ring, hydroxyguanidine, and imine groups was important for this set. By contrast, for set B molecules the acceptor activity was most influenced by the geometry of methoxy groups and the size and geometry of meta and para substituents of the phenyl ring.

Original languageEnglish
Pages (from-to)3105-3110
Number of pages6
JournalJournal of Medicinal Chemistry
Volume47
Issue number12
DOIs
Publication statusPublished - 3 Jun 2004
Externally publishedYes

Field of Science

  • 3.1 Basic medicine

Publication Type

  • 1.1. Scientific article indexed in Web of Science and/or Scopus database

Fingerprint

Dive into the research topics of 'Synthesis and quantitative structure-activity relationship of hydrazones of N-amino-N′-hydroxyguanidine as electron acceptors for xanthine oxidase'. Together they form a unique fingerprint.

Cite this