ABSTRACT
The influence of methimazole (MTI) on the mitogenic proliferation of human blood lymphocytes was studied in vitro to evaluate the potential immunomodulatory activity of this antithyroid drug. The effects of the drug on the lymphocyte cell cycle were assessed by multiparametric flow cytometry. Although MTI induced an increase in the number of lymphocytes in the synthesis and G2M compartments, it failed to stimulate proliferation as the cells tended to accumulate in the quiescent S compartment. The effect was dose-dependent over a range from 0.1 to 100 mM. These in vitro results indicate that MTI possesses immunosuppressive activity.
Subject(s)
Immunosuppressive Agents/pharmacology , Lymphocyte Activation/drug effects , Methimazole/pharmacology , S Phase/drug effects , Adult , Bromodeoxyuridine , Cells, Cultured , DNA/biosynthesis , Flow Cytometry/methods , Flow Cytometry/statistics & numerical data , Humans , Propidium , Staining and LabelingABSTRACT
A series of new 2-pyridyl-2-thiobenzoxazole and 2-pyridyl-2-thiobenzimidazole compounds was prepared and investigated by a number of in vitro methods in order to determine their prostaglandin synthesis inhibitory activity. The most active compound decreases prostaglandin production and carrageenin edema, but has a less platelet antiaggregatory activity.
Subject(s)
Arachidonic Acid/metabolism , Benzimidazoles/chemical synthesis , Benzoxazoles/chemical synthesis , Prostaglandin Antagonists/chemical synthesis , Animals , Anti-Inflammatory Agents, Non-Steroidal/pharmacology , Benzimidazoles/pharmacology , Benzoxazoles/pharmacology , Dinoprostone/metabolism , Edema/chemically induced , Edema/prevention & control , Humans , In Vitro Techniques , Male , Platelet Aggregation/drug effects , Platelet Aggregation Inhibitors/chemical synthesis , Platelet Aggregation Inhibitors/pharmacology , Prostaglandin Antagonists/pharmacology , Rats , Rats, Wistar , Synovial Fluid/drug effectsABSTRACT
1. The comparative effects of methimazole (MTI), an antithyroid drug, and its S-methyl derivate (MMTI), were studied in vitro on the lymphoproliferative response to lectin in order to point out the free SH group importance. The cell cycle analysis was performed by flow cytometry after cellular DNA staining by propidium iodide. 2. We showed that MTI enhanced the PHA-induced DNA synthesis phase (P < 0.05 from 1 to 100 microns) whereas MMTI had no significant activity. The free SH group seems to be necessary to the MTI immunomodulatory activity.
Subject(s)
Lymphocytes/drug effects , Methimazole/pharmacology , Adult , Cell Cycle , Cells, Cultured/drug effects , Dose-Response Relationship, Drug , Flow Cytometry , Humans , In Vitro Techniques , Lectins/pharmacology , Methimazole/metabolismABSTRACT
A series of compounds based on the structure of MTI (1-methyl-2-thioimidazole) were synthesized by condensation of alpha-hydroxyketones and alkylthioureas. The alpha-hydroxyketones were obtained by a radical reaction in the presence of sodium and the alkyl ester, while the alkylthioureas were prepared by nucleophilic addition of ammonia on an alkylisothiocyanate. The antithyroid activity of the 13 compounds prepared was evaluated in vitro by determination of the concentrations which led to a 50% inhibition (IC50) of the activity of thyroid peroxidase, and in vivo by assay of thyroid hormones levels and histological examination of the thyroid gland in rats treated chronically with the compounds. 1-methyl-4,5-dipropyl 2-thioimidazole (compound 10) was found to have the highest antithyroid activity of the 13 compounds synthesized.
Subject(s)
Antithyroid Agents/chemical synthesis , Imidazoles/chemical synthesis , Animals , Antithyroid Agents/pharmacology , Imidazoles/pharmacology , In Vitro Techniques , Iodide Peroxidase/antagonists & inhibitors , Lactoperoxidase/antagonists & inhibitors , Magnetic Resonance Spectroscopy , Male , Rats , Rats, Wistar , Spectrophotometry, Infrared , Thyroid Gland/chemistry , Thyroid Gland/drug effectsABSTRACT
New 1,4,5-trialkyl-2-thioimidazole have been synthesized by the condensation of alpha-hydroxyketones and alkylthioureas. The in vitro platelet aggregation inhibiting effect of prepared compounds on human platelets was studied in the presence of ADP and collagen as inducers. The formation of thromboxane B2(TXB2) was inhibited. 1-isopropyl-4,5-dimethyl-2-thioimidazole has the greatest aggregation inhibiting effect, about 4 times that of aspirin. It highly inhibits the production of TXB2 (68.5% for a final concentration of 0.04 M).
Subject(s)
Imidazoles/chemical synthesis , Platelet Aggregation Inhibitors/chemical synthesis , Platelet Aggregation/drug effects , Aspirin/pharmacology , Humans , Imidazoles/pharmacology , In Vitro Techniques , Platelet Aggregation Inhibitors/pharmacology , Thromboxane B2/biosynthesis , Thromboxane B2/bloodABSTRACT
In an investigation of the anti-inflammatory properties of five-membered ring nitrogen-containing heterocyclic compounds, two series of derivatives of imidazole were prepared by altering the sites of substitution and by joining aliphatic chains to the nitrogen atom in the 1 position of the imidazole ring. Some of them were more potent inhibitors of carrageenan-induced edema than indomethacin. An electron spin resonance study indicated that these compounds possess anti-radical activity.
