Synthesis of guanidino analogues of PMPDAP and their immunobiological activity.
A series of novel 9-, 7- and 3-substituted 2- or 6-guanidinopurines as analogues of potent antiviral and immunobiologically active compound enantiomers of PMPDAP was synthesized and evaluated for their biological activity. Compounds containing the combination of guanidino and amino group at the purine moiety enhanced the interferon-gamma-triggered NO production in murine macrophages and stimulated the secretion of cytokines and chemokines in both murine macrophages and human peripheral blood mononuclear cells. The most active compounds are 27 and 54. None of the compounds tested exhibited any significant cytostatic effect or antiviral effect.
Cesnek
Michal
M
Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, v.v.i., Flemingovo nám. 2, 166 10 Praha 6, Czech Republic. cesnek@uochb.cas.cz
Holý
Antonín
A
Masojídková
Milena
M
Kmonícková
Eva
E
Zídek
Zdenek
Z
D000225:Adenine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000276:immunology; D000276:Adjuvants, Immunologic / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D000818:Animals; D018925:Chemokines / Q000032:analysis / Q000097:blood; D020650:Combinatorial Chemistry Techniques; D016207:Cytokines / Q000032:analysis / Q000097:blood; D005260:Female; D006146:Guanidines / Q000138:chemical synthesis / Q000737:chemistry / Q000276:immunology; D006801:Humans; D017737:Macrophages, Peritoneal / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D015394:Molecular Structure; D009569:Nitric Oxide / Q000032:analysis / Q000096:biosynthesis; D009943:Organophosphorus Compounds / Q000138:chemical synthesis / Q000737:chemistry / Q000276:immunology; D013237:Stereoisomerism
C090125:9-(2-phosphonylmethoxypropyl)-2,6-diaminopurine; D000276:Adjuvants, Immunologic; D018925:Chemokines; D016207:Cytokines; D006146:Guanidines; D009943:Organophosphorus Compounds; D009569:Nitric Oxide; D000225:Adenine