Synthesis and immunological activity of mono- and disubstituted derivatives of 2,5-dimercapto-1,3,4-thiodiazoles.

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.

Immunotropic activities of benzisoselenazolones and organic diselenides in mice.

We have investigated the immunotropic effects of 23 seleno-organic compounds (8 benzisoselenazolones, 3 benzisoselenazolone oxides and 12 organic diselenides). All of the compounds increased the rosette formation of sheep red blood cells (SRBC) with spleen cells obtained from thymectomized C53BL/6 mice and incubated in vitro in the presence of imuran. Furthermore, 16 of the compounds were also assayed in vitro in the hydrocortisone test performed with C57BL/6 mouse thymocytes.

Studies on the effect of organophosphorus pesticide phosalone on mouse immune system.

The effect of an organophosphorus pesticide-phosalone on some parameters of humoral and cellular immunologic response in mice was investigated. Haematological and morphological examinations were made parallelly. It was found that immunotropic effect of phosalone was a reversible process.

Immunotropic activity of lupin seeds extracts and fractions from Lupinus angustifolius and Lupinus albus.

The results demonstrated immunotropic activity of seeds extracts and fractions from Lupinus angustifolius and Lupinus albus. Plaque forming cells (PFC) number to SRBC (sheep red blood cells) were elevated by an extract from Lupinus angustifolius and lowered by extracts from Lupinus albus. All preparations obtained from Lupinus angustifolius reduced the number of rosette forming cells (E-RFC).

The toxicity of seed extracts and their fractions from Lupinus angustifolius L. and Lupinus albus L.

Seed extracts obtained from Lupinus albus and Lupinus angustifolius by treatment with 48% ethanol contained ca. 10% alkaloids (on a dry weight basis) and were non-toxic. Their acute toxicity (LD50) in the mouse is > 4000 mg kg-1 body wt.

Studies on effect of pesticide Chlorfenwinfos on mouse immune system.

The effect of organophosphate pesticide--Chlorfenwinfos on the selected parameters of humoral and cellular immunologic response in mice was investigated. Hematologic and histologic examinations were run parallelly. The animals were treated with pesticide p.

Synthesis and immunological activity of dialkyloamine- and N-piperidinederivatives of dithiocarbamic acid.

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.

Synthesis and immunopharmacological analysis of selected butanic and butanodionic acid amides containing aziridine unit. II.

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.

Synthesis and immunopharmacological analysis of selected derivatives of N,N'-bis-/3-aziridine/butanoylalkylenediamines and imides of 3-aziridinesuccinic acid. I.

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.

Studies on affinity of pesticide Unden--2-isopropoxyphenyl N-methylcarbamate to immunological system.

The effect of 2-isopropoxyphenyl methylcarbamate (Unden) (10- or 30-day exposure) on the selected parameters of humoral and cellular immunological response in mice was investigated. Hematologic and histologic examinations were run parallelly. It was noted that this compound exerts immunotropic effect.

Immunopharmacological indices of piroxicam.

The activity of piroxicam to the selected cellular immune reactions was studied. The drug was shown to modulate these processes, with the prevailing role of suppressive component. It was found that the mechanism of its effect partly consists in an interference in the activity of suppressor cells and mediators of immunological reactions.

Immunological profile of animals exposed to pesticide--deltamethrin.

The effect of deltamethrin (10- or 30-day exposure) on selected parameters of humoral and cellular immune response in mice was studied. In parallel also hematologic and histologic examinations were performed. It was found that deltamethrin exerts negligible immunotropic effect.

Studies on aziridine derivatives. III. Synthesis and immunopharmacological activity of aziridine derivatives of propionic acid.

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.

Pharmacological investigations on anti-inflammatory activity of tryptamide (3-nicotinoyl-tryptamine).

The study concerned anti-inflammatory activity of a new tryptamine derivative - tryptamide. This preparation was effective in nonspecific inflammations and those involving immune mechanisms. Only postadjuvant inflammation appeared resistant to its effect.

Studies on the derivatives of aziridine. II. Synthesis and immunopharmacological analysis of substituted amides and anilides of alpha-aziridinyl-beta-/p-chlorobenzoyl/-propionic acid.

Several new amides and anilides of alpha-aziridinyl-beta-/p-chlorobenzoyl/-propionic acid were synthetized. The beta-/p-chlorobenzoyl/-acrylic acid 2 was used as the substrate. This compound was converted by reaction with appropriate amine into amides and anilides of beta-/p-chlorobenzoyl/-acrylic acid (3-10).

Immunobiological and antiinflammatory properties of 1-phenylo-2-thioxo-3-diethylo-aminoethylo-4-ox o-7-methylpyrimido- [4,5-c]-pyrimidine hydrochloride (compound I).

Immunological and pharmacological properties of 1-phenylo-2-thioxo-3-diethylo-aminoethylo-4-oxo- 7-methylpyrimido [4,5-c]-pyrimidine hydrochloride were evaluated. The preparation was observed to exert immunotropic, predominantly suppressive effect as well as nonspecific antiinflammatory effect. This was accompanied by hardly perceptible central component and slight, reversible effect on the circulatory system.

Studies on the derivatives of aziridine. I. synthesis and immunopharmacological analysis of amides of alpha-aziridinyl- beta-/p-chlorobenzoyl/-propionic acid.

Several new aziridinyl derivatives of beta-/p-chlorobenzoyl/propionic acid were synthesized (3, 5, 7, 14-18). The gamma-/p-chlorophenyl/-dihydrofuran-2-one 2 and beta-/p-chlorobenzoyl/acrylic acid 4 were used as the substrates. Compound 2 reacts with ethylenimine yielding aziridinylamide of beta-/p-chlorobenzoyl/-propionic acid 3.

[The influence of immunomodulators on lymphokine secretion of radiation-damaged lymphocytes].

Spleen lymphocytes derived from guinea pigs loose their ability to secrete lymphokines induced by Con A after treatment with irradiation (500 and 750 mC/kg). In the presence of the immunomodulator isoprinosine, levamisole and the thymosine-like factor TFX the lymphocytes are again capable of secreting lymphokines. After treatment with isoprinosine, levamisole and TFX in dosages between 10 and 100 micrograms/ml the migration inhibition activity for macrophages and the chemotactic activity for polymorphonuclear granulocytes produced by lymphocytes were restored.

Pharmacological activity of 3-(5-barbiturylo)-propanesulfonic acids derivatives.

Pharmacological activity of 6 newly synthetized water-soluble derivatives of barbiturylo propanosulfonic acids, was evaluated. The compounds were obtained under the conditions of the Ritter reaction. The experiments were performed with the aim to determine the anti-inflammatory and immunotropic activities as well as the central action of the new derivatives; indomethacin was a reference preparation.

Chemical, pharmacological and oncostatic properties of 5-(4'-hydroxybenzylidenoimino)-4, 6-diketo-4, 5, 6, 7-tetrahydropyrimidine-[4, 5-d]-3-methyl-isothiazole (compound IP-10).

Advanced preclinical studies on IP-10 preparation (4,6-diketo-4, 5, 6, 7-tetrahydropyrimidine-[4, 5-d]-3-methyl-isothiazole) were carried out. The drug was shown to be devoid of the irritating local effect, mildly toxic and hardly absorbing when administered per os. The toxic effect showed tendency toward cumulation.

Syntheses and pharmacological analysis of new derivatives of tetrahydro-[1,3]-thiazine and 2-thiobarbituric acid.

Three groups of compounds:1,3-thiazine derivatives, 2-thiobarbituric acid derivatives and noncyclic thioureide were obtained as a result of condensation of some N, N1-derivatives of thiocarbamide and malonyl dichlorides, depending on the reaction conditions and chemical character of reagents. It was observed that the substituents beside nitrogen atoms of thiocarbamides, the kind of acid chloride and reaction conditions influenced the course of reaction. The structure of the newly synthesized compounds was proved by the analysis of PMR spectrum and the interpretation of IR spectrum.

Pharmacological studies on p-chlorophenylamide of 3-methyl-5-benzoylaminoizothiazole-4-carboxylic acid (compound ITCL) the preparation of eventual anti-inflammatory effect.

Pharmacological activity of p-chlorophenylamide of 3-methyl-5-benzoylaminoizothiazole-4-carboxylic acid (compound ITCl) was studied with special regard to its anti-inflammatory effect. Compound ITCl is moderately toxic with no distinct circulatory and central effect. On the other hand, it shows strong anti-inflammatory activity in many tests of immunologically specific, nonspecific and infectious inflammations.