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ID: ALA1146160

Journal: Bioorg Med Chem Lett

Title: Synthesis and evaluation of some lipidic aminoalcohols and diamines as immunomodulators.

Authors: del Olmo E, Plaza A, Muro A, Martínez-Fernández AR, Nogal-Ruiz JJ, López-Pérez JL, Feliciano AS.

Abstract: 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.

CiteXplore: 17000108

DOI: 10.1016/j.bmcl.2006.08.113