Phosphatidyl myo-inositol mannosides mimics built on an acyclic or heterocyclic core: synthesis and anti-inflammatory properties.

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Front, Sophie | Court, Nathalie | Bourigault, Marie-Laure | Rose, Stéphanie | Ryffel, Bernhard | Erard, François | Quesniaux, Valérie | Martin, Olivier R

Edité par CCSD ; Wiley-VCH Verlag -

International audience. 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.

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