[Immunomodulator structure-activity relationships: contribution of molecular modeling]. / Relations structures-activités des immunomodulateurs. Apport de la modélisation moléculaire.

Molecular modeling used to compare 64 immunostimulant compounds with pyrrolie quinolein or purine nuclei has pointed out that a common spatial structure is found in most of the active compounds. An additional study of immunostimulants (levamisole, muramyldipeptide) or immunosuppressive molecules (rapamycin) was performed. A common pharmacophore was found on every studied compound. It was composed of three neighboring electroattractive atoms and a further fourth atom. The favorable conformation of rapamycin for immunosuppressive action, which is not the more stable conformation, could explain the loss of its activity, or those of related macrolides, when some minor chemical modifications are tested. These findings validate the proposed concept and provide a view of the mechanism of action of most of the immunomodulator compounds for preparing novel compounds