title: Phosphatidyl myo-inositol mannosides mimics built on an acyclic or heterocyclic core: synthesis and anti-inflammatory properties.
abstract: 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.
authors: ICOA, UMR 6005, Université d'Orléans and CNRS rue de Chartres, B. P. 6759, 4067 Orléans, France.
authors: Sophie
authors: S
authors: Front
authors: Nathalie
authors: N
authors: Court
authors: Marie-Laure
authors: ML
authors: Bourigault
authors: Stéphanie
authors: S
authors: Rose
authors: Bernhard
authors: B
authors: Ryffel
authors: François
authors: F
authors: Erard
authors: Valérie F J
authors: VF
authors: Quesniaux
authors: Olivier R
authors: OR
authors: Martin
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000737:chemistry* / Q000494:pharmacology*; D016207:Cytokines / Q000276:immunology / Q000378:metabolism; D004353:Drug Evaluation, Preclinical; D005260:Female; D007294:Inositol / Q000737:chemistry; D008070:Lipopolysaccharides / Q000494:pharmacology; D008264:Macrophages / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D051379:Mice; D018716:Molecular Mimicry; D009569:Nitric Oxide / Q000378:metabolism; D010716:Phosphatidylinositols / Q000737:chemistry* / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D000893:Anti-Inflammatory Agents; D016207:Cytokines; D008070:Lipopolysaccharides; D010716:Phosphatidylinositols; C034154:phosphatidylinositol mannoside; D009569:Nitric Oxide; D007294:Inositol