ABSTRACT
It is presented that the newly synthesized mono- and disubstituted 2,5-dimercapto-1,3,4-thiodiazole derivatives exert immunotropic activity. This effect was evaluated by measuring plaque forming cell number, circulating immunoglobulins level, autologous rosette number, mitogenic activity and by performing popliteal lymph node assay. It is shown that intensity of immunotropic activity depends on chemical structure: mono-substituted derivatives had a strong suppressive effect, disubstituted compounds showed the variable activity. One compound of this group exerted a stimulatory effect. The tested compounds were active in popliteal lymph node assay and had no mitogenic activity.
Subject(s)
Immunosuppressive Agents/chemical synthesis , Animals , Carbamates/chemical synthesis , Female , Immunosuppressive Agents/pharmacology , Lethal Dose 50 , Lymphocyte Activation/drug effects , Male , Mice , Mice, Inbred BALB C , Rosette Formation , Structure-Activity RelationshipABSTRACT
A series of aminocarbamic acid derivatives, containing fragments of substituted hydrazine and dithiocarbamic acid, was synthesized. The immunopharmacologic studies showed these that derivatives exerted immunotropic, mainly suppressive effects (PFC, circulating immunoglobulins, E-RFC, A-RFC). Some of these compounds, however, caused significant increase of weight of the popliteal lymph nodes. The immunotropic activity of the newly synthesized preparations is comparable with the action of sodium diethyldithiocarbamate (imuthiol).
Subject(s)
Immunosuppressive Agents/pharmacology , Thiocarbamates/pharmacology , Adjuvants, Immunologic/chemical synthesis , Adjuvants, Immunologic/chemistry , Adjuvants, Immunologic/pharmacology , Animals , Antibody-Producing Cells/drug effects , Ditiocarb/pharmacology , Female , Immunoglobulin M/blood , Immunosuppressive Agents/chemical synthesis , Immunosuppressive Agents/chemistry , Lymph Nodes/drug effects , Male , Mice , Mice, Inbred A , Mice, Inbred C57BL , Molecular Structure , Rosette Formation , Structure-Activity Relationship , Thiocarbamates/chemical synthesis , Thiocarbamates/chemistryABSTRACT
A series of aziridinederivatives of N,N'-bis-butanoylalkylenodiamines (Scheme 1, 1-4) and aziridinederivatives of substituted succinic acid (Scheme 2, 16-19) was obtained. Pharmacological analysis revealed that these compounds were immunotropic, of marked suppressive effect (PFC, RFC, circulating immunoglobulins). Outstanding in this group was phenyloimide of succinic acid (prep. 16) which reduced PFC and RFC number but increased the level of circulating IgG.
Subject(s)
Aziridines/pharmacology , Immunosuppressive Agents/pharmacology , Animals , Antibody-Producing Cells/drug effects , Aziridines/chemical synthesis , Aziridines/chemistry , Drug Evaluation, Preclinical , Immunoglobulin G/metabolism , Immunoglobulin M/metabolism , Immunosuppressive Agents/chemical synthesis , Immunosuppressive Agents/chemistry , Mice , Mice, Inbred Strains , Molecular Structure , Rosette Formation , Structure-Activity RelationshipABSTRACT
In the reaction of butanic and butanodionic acid chlorides with amines, amides 1-10 were produced. Addition of aziridine to a double bonds was performed in alkaline medium which resulted in aziridine derivatives of both acids. Pharmacological study revealed that the preparations examined possess immunotropic, strongly suppressive activity (PFC, E-RFC), partly IgG level; they leave the titer of circulating IgM unchanged. It seems that rather the basic system of acids than the substituents introduced to it are responsible for the effect of the compounds.
Subject(s)
Aziridines/pharmacology , Immunosuppressive Agents/pharmacology , Animals , Antibody-Producing Cells/drug effects , Aziridines/chemical synthesis , Aziridines/chemistry , Drug Evaluation, Preclinical , Immunoglobulin G/metabolism , Immunoglobulin M/metabolism , Immunosuppressive Agents/chemical synthesis , Immunosuppressive Agents/chemistry , Mice , Mice, Inbred Strains , Molecular Structure , Rosette Formation , Structure-Activity RelationshipABSTRACT
Several new aziridine derivatives of propionic acid were synthesized (10-15, 19, 20). o-, m-, p-Chloroanilide of chloroacetic acid 1-3 and chloride of 3-/p-chlorobenzoyl/acrylic acid 16 were the substrates. The compounds 1-3 in reaction with nicotine aldehyde or p-chlorobenzaldehyde were transformed into appropriate anilides of 2,3-epoxypropionic acid 4-9. These, in turn reacted with ethylenimine giving the appropriate 3-aziridine derivatives 10-15. Acid chloride 16 in reaction with amines gave the appropriate amides 17 and 18 which formed 2-aziridine derivatives 19 and 20 when under the influence of ethylenimine. Pharmacological analysis revealed that the aziridine derivatives 12-15, 19 and 20 modulate some immunological reactions with the prevailing effect of the suppressive component (PFC, RFC, IgM level, cellular response to SRBC). The stimulatory effect was observed with some compounds on the level of circulating IgG and GvH reaction. The mechanism of these compounds consists in their interference with the activity of Ts cells and mediators of the immunological reactions.
Subject(s)
Aziridines/metabolism , Azirines/metabolism , Graft vs Host Reaction/drug effects , Immunosuppressive Agents , Propionates/metabolism , Animals , Aziridines/pharmacology , Aziridines/toxicity , Interleukin-1/metabolism , Mice , Mice, Inbred BALB C , Molecular Conformation , Propionates/pharmacology , Viral Plaque AssaySubject(s)
Arterial Occlusive Diseases/etiology , Embolism/etiology , Adult , Aged , Arterial Occlusive Diseases/surgery , Embolism/surgery , Female , Humans , Male , Middle Aged , RecurrenceABSTRACT
The action of acetyl chloride on 2-carboxy-7-hydroxychromanone-4 (I) gives rise to a compound with structure 2-chlorocarbonylmethane-3,6-diacetoxybenzo-(b)-furan (II). Chloride (II) was used to obtain amides IV--XI. Pharmacologic screening of chromanone derivatives showed strongest anti-inflammatory activity of 2-(2,4-dichloroanilido)- and 2-cyclohexylamido-3,6-diacetoxybenzo-(b)-furan (compounds 9 and 10), and much weaker anti-inflammatory activity of the remaining compounds.
