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Phosphatidyl myo ‐Inositol Mannosides Mimics Built on an Acyclic or Heterocyclic Core: Synthesis and Anti‐inflammatory Properties
Author(s) -
Front Sophie,
Court Nathalie,
Bourigault MarieLaure,
Rose Stéphanie,
Ryffel Bernhard,
Erard François,
Quesniaux Valérie F. J.,
Martin Olivier R.
Publication year - 2011
Publication title -
chemmedchem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.817
H-Index - 100
eISSN - 1860-7187
pISSN - 1860-7179
DOI - 10.1002/cmdc.201100291
Subject(s) - cyclitol , moiety , chemistry , stereochemistry , tetrahydropyran , inositol , anti inflammatory , piperidine , biochemistry , ring (chemistry) , receptor , organic chemistry , biology , pharmacology
Phosphatidyl myo ‐inositol mannosides (PIMs) are constituents of the mycobacterial cell wall and possess immunomodulatory activities. Certain PIM derivatives have immunoprotective activity and are of interest as anti‐inflammatory agents. In order to identify simplified analogues of PIMs that retain this interesting activity, we have prepared a series of new analogues based either on an acyclic or on a heterocyclic scaffold that replaces the inositol moiety, and evaluated these compounds for their inhibition of LPS‐induced release of NO and pro‐inflammatory cytokines by macrophages. It was found that the inositol moiety can be favourably replaced by an aza‐cyclitol (trihydroxy‐piperidine) or an oxa‐cyclitol (trihydroxy‐tetrahydropyran) unit, and that the configuration of the OH‐carrying carbons does not play a significant role. The biological activity is reduced if the nitrogen atom is free in the aza‐cyclitol unit.