Synthesis and immunomodulatory activites of new 5-hydrazino-3-methyl-4-isothiazolecarboxylic acid ethyl esters.
Several new derivatives of 5-hydrazino-3-methyl-4-isothiazolecarboxylic ethyl esters were synthesized. Using 4-aminoacetophenone, the hydrazine group was transformed in position 5 in the hydrazone which reacted with the isocyanates, aldehydes and sugars. Thirteen newly synthesized compounds were tested for their ability to affects the immunological response in vitro in several rodent models. The immunoregulatory properties of the compounds were differential and dose-dependent. The strongest activity was exhibited by 5-{N'-[1-4{-4-[3-(-methoxyphenyl)-ureidol]-phenylethylidene]-hydrazino}-3-methyl-4-isothiazolecarboxylic acid ethyl ester (compound 3a). The compound strongly inhibited the secondary, humoral immune response to sheep erythrocytes and the proliferative response of mouse splenocytes to concanavalin A and pokeweed mitogen. The immunotropic activities of the new isothiazole derivatives and potential application of the compounds in therapy are discussed.
Lipnicka
Urszula
U
Wrocław Medical University, Faculty of Pharmacy, Department of Organic Chemistry, Grodzka 9, 50-137 Wrocław, Poland. urszula@chorg.am.wroc.pl
Maczyński
Marcin
M
Artym
Jolanta
J
Zimecki
Michał
M
D000818:Animals; D001402:B-Lymphocytes / Q000187:drug effects / Q000276:immunology; D002264:Carboxylic Acids / Q000008:administration & dosage / Q000138:chemical synthesis / Q000494:pharmacology*; D003208:Concanavalin A; D004305:Dose-Response Relationship, Drug; D004912:Erythrocytes / Q000187:drug effects / Q000276:immunology; D007155:Immunologic Factors / Q000008:administration & dosage / Q000138:chemical synthesis / Q000494:pharmacology*; D051379:Mice; D008808:Mice, Inbred CBA; D011043:Pokeweed Mitogens; D051381:Rats; D017208:Rats, Wistar; D012756:Sheep; D013154:Spleen / Q000166:cytology / Q000187:drug effects; D013329:Structure-Activity Relationship; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D013844:Thiazoles / Q000008:administration & dosage / Q000138:chemical synthesis / Q000494:pharmacology*
D002264:Carboxylic Acids; D007155:Immunologic Factors; D011043:Pokeweed Mitogens; D013844:Thiazoles; D003208:Concanavalin A