Synthesis and evaluation of some lipidic aminoalcohols and diamines as immunomodulators

Lymphoproliferation inhibition and cytotoxicity of a number of lipidic aminoacids, aminoalcohols and diamines were evaluated as a preliminary screening to select potential immunomodulators. The four most potent/less toxic compounds were submitted to delayed hypersensibility (DTH) assays to define the best to be evaluated further Graft-vs-Host, NO production and other immunoevaluation (CD4+, CD45, CD8, CD11b, I-Ek, and NK cells) assays, to establish their immunomodulation potential for being further considered as auxiliary agents for vaccination against some parasitic infections. Compounds 5d, 6d, 6f, 7a, and 9a, fairly inhibited the lymphoproliferation (71.6–79.5%, at 3.2–2.4 nM), while the aminoalcohol derivative 6f and the diamine 7a gave the most promising results in the DTH assays. Diamine derivative 8b induced nitrite production on normal macrophages, whereas compounds 6f and 7a induced nitrite production on LPS pre-stimulated macrophages. These two last compounds have been selected to follow in vivo vaccination assays.

Graphical abstractLymphoproliferation inhibition and delayed hypersensibility assays have served to select primarily the compounds to be evaluated further, through Graft-vs-Host reaction, NO production and other assays, in order to determine the potential of the title compounds for being used as immunomodulators.Figure optionsDownload full-size imageDownload as PowerPoint slide