Synthesis, immunological activity and computational study of 5-amino-3-methyl-4-isoxazolecarboxylic acid semicarbazides and thiosemicarbazides.
A series of 5-amino-3-methyl-4-isoxazolecarboxylic acid semicarbazides and thiosemicarbazides (M1-M9) were obtained by reacting 5-amino-3-methyl-4-isoxazolecarboxylic acid hydrazide with isocyanate and isothiocyanate. In order to determine structure-activity relationships for the series of nine compounds (M1-M9) geometry optimization was carried out using quantum-chemical DFT calculations at B3LYP/6-31g* level. The compounds, administered to mice at 1 microg or 10 microg doses, four hours prior to immunization with sheep erythrocytes (SRBC), significantly suppressed the primary, humoral immune response in mice as measured by the number of antibody-forming cells (AFC) in the spleens. Structure/activity relationships, regarding the studied compounds, were discussed.
Maczyński
Marcin
M
Wrocław Medical University, Faculty of Pharmacy, Department of Organic Chemistry, 50-137 Wrocław, 9 Grodzka Str., Poland. marcinm@chorg.am.wroc.pl
Zimecki
Michał
M
Taraszkiewicz
Magdalena
M
Ryng
Stanisław
S
D000818:Animals; D000917:Antibody Formation / Q000187:drug effects; D007166:Immunosuppressive Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D051379:Mice; D008808:Mice, Inbred CBA; D021281:Quantitative Structure-Activity Relationship; D012663:Semicarbazides / Q000138:chemical synthesis* / Q000494:pharmacology
D007166:Immunosuppressive Agents; D012663:Semicarbazides; C005151:thiosemicarbazide