Synthesis and immunobiological activity of base substituted 2-amino-3-(purin-9-yl)propanoic acid derivatives.
2-Amino-3-(purin-9-yl)propanoic acids substituted at position 6 of the purine base moiety by dimethylamino, cyclopropylamino, pyrrolidin-1-yl, hydroxy, and sulfanyl group as well as their 2-aminopurine analogues were prepared from corresponding 9-(2,2-diethoxyethyl)purines and 2-aminopurines, respectively, by the Strecker synthesis. 2-Aminopropanoic acid derivatives were tested for their immunostimulatory and immunomodulatory potency. Some of these compounds significantly enhanced secretion of chemokines RANTES and MIP-1alpha, the most potent was 2-amino-6-sulfanylpurine derivative. Most of these compounds also augmented NO biosynthesis triggered primarily by IFN-gamma.
Doláková
Petra
P
Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, Prague, Czech Republic. dolakova@uochb.cas.cz <dolakova@uochb.cas.cz>
Holý
Antonín
A
Zídek
Zdenek
Z
Masojídková
Milena
M
Kmonícková
Eva
E
D000818:Animals; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D018946:Chemokine CCL5 / Q000276:immunology / Q000378:metabolism; D005260:Female; D007159:Immunologic Tests; D007371:Interferon-gamma / Q000494:pharmacology; D019402:Macrophage Inflammatory Proteins / Q000276:immunology / Q000378:metabolism; D008264:Macrophages / Q000187:drug effects / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D015394:Molecular Structure; D009569:Nitric Oxide / Q000096:biosynthesis; D011422:Propionates / Q000138:chemical synthesis* / Q000276:immunology / Q000494:pharmacology*; D013329:Structure-Activity Relationship
D054405:Chemokine CCL3; D054407:Chemokine CCL4; D018946:Chemokine CCL5; D019402:Macrophage Inflammatory Proteins; D011422:Propionates; D009569:Nitric Oxide; D007371:Interferon-gamma