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.
del Olmo
Esther
E
Departamento de Química Farmacéutica, Facultad de Farmacia, CIETUS, Universidad de Salamanca, 37007 Salamanca, Spain. olmo@usal.es <olmo@usal.es>
Plaza
Alvaro
A
Muro
Antonio
A
Martínez-Fernández
Antonio R
AR
Nogal-Ruiz
Juan J
JJ
López-Pérez
José L
JL
Feliciano
Arturo San
AS
D000605:Amino Alcohols / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology* / Q000633:toxicity; D049109:Cell Proliferation / Q000187:drug effects; D003959:Diamines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology* / Q000633:toxicity; D057927:Hydrophobic and Hydrophilic Interactions; D007155:Immunologic Factors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity; D015394:Molecular Structure; D009573:Nitrites / Q000378:metabolism; D013329:Structure-Activity Relationship
D000605:Amino Alcohols; D003959:Diamines; D007155:Immunologic Factors; D009573:Nitrites