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Oxidation of anti-thyroid drugs and their selenium analogs by ABTS radical cation
Frackowiak-Wojtasek, Bozena ; Gasowska-Bajger, Beata ; Tarasek, Damian , et al. Bioorg. Chem.,2023,141,106891. DOI: 10.1016/j.bioorg.2023.106891 PubMed ID: 37788560
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Abstract: Lactoperoxidase was previously used as a model enzyme to test the inhibitory activity of selenium analogs of anti-thyroid drugs with 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) as a substrate. Peroxidases oxidize ABTS to a metastable radical ABTS.+, which is readily reduced by many antioxidants, including thiol-containing compounds, and it has been used for decades to measure antioxidant activity in biol. samples. We showed that anti-thyroid drugs 6-n-propyl-2-thiouracil, methimazole, and selenium analogs of methimazole also reduced it rapidly. This reaction may explain the anti-thyroid action of many other compounds, particularly natural antioxidants, which may reduce the oxidized form of iodine and/or tyrosyl radicals generated by thyroid peroxidase thus decreasing the production of thyroid hormones. However, influence of selenium analogs of methimazole on the rate of hydrogen peroxide consumption during oxidation of ABTS by lactoperoxidase was moderate. Direct hydrogen peroxide reduction, proposed before as their mechanism of action, cannot therefore account for the observed inhibitory effects. 1-Methylimidazole-2-selone and its diselenide were oxidized by ABTS.+ to relatively stable seleninic acid, which decomposed slowly to selenite and 1-methylimidazole. In contrast, oxidation of 1,3-dimethylimidazole-2-selone gave selenite and 1,3-dimethylimidazolium cation. Accumulation of the corresponding seleninic acid was not observed
Keywords: Methimazole ; n -Propyl-2-thiouracil ; Lactoperoxidase ; Horseradish peroxidase ; Selenium ; ABTS
CAS No. : | 60-56-0 | MDL No. : | MFCD00179321 |
Formula : | C4H6N2S | Boiling Point : | - |
Linear Structure Formula : | C3H2N2(SH)(CH3) | InChI Key : | PMRYVIKBURPHAH-UHFFFAOYSA-N |
M.W : | 114.17 | Pubchem ID : | 1349907 |
Synonyms : |
Thiamazole;NSC 38608;Northyx;Favistan
|
Chemical Name : | 1-Methyl-1H-imidazole-2(3H)-thione |
Signal Word: | Warning | Class: | N/A |
Precautionary Statements: | P201-P202-P261-P272-P280-P302+P352+P333+P313+P363-P308+P313-P405-P501 | UN#: | N/A |
Hazard Statements: | H303-H317-H361 | Packing Group: | N/A |
GHS Pictogram: |
* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
97% | With triethylamine; In acetonitrile; at 20℃; | Et3N (0.239 mL, 0.98 mmol) was added to a solution of 2-bromo-l-(2,4,6-trimethyl- phenyl)-ethanone (208 mg, 0.86 mmol) and 2-mercapto-l-methylimidazole (98 mg, 0.86 mmol) in CH3CN (8 mL) at room temperature. The reaction was stirred overnight at room temperature then was quenched with of a saturated solution OfNH4Cl. The extraction was conducted with DCM (x2) then the organic phase was washed with brine and dried over MgSO4. The crude residue was the purified by flash chromatography (hexane/EtOAc 0- 40% gradient) to afford the expected compound (229 mg, 97%) as yellow oil. TLC single spot at R/ 0.23 (hexane/EtOAc 6:4); 1H NMR (270 MHz, CDCl3): delta 2.10 (s, 6H), 2.25 (s, 3H), 4.32 (s, 2H), 6.79 (s, 2H), 6.87 (s br, IH), 7.00 (s br, IH); LC/MS (APCI) m/z 275 (M++H); HPLC tr = 1.99 min (99.5%) in 10% water-acetonitrile. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
72% | With Lawessons reagent; In toluene; for 18h;Inert atmosphere; Reflux; | In a dry 500 ml reaction flask,1-methyl-1,3-2H-imidazol-2-one was added under nitrogen and 110 g of Lawesson's reagent was added followed by 145 g of toluene followed by nitrogenGas protection under reflux reaction 18 hours; sample HPLC control to the reaction completely; the reaction is complete, vacuum distillationAfter distilling the toluene to one-third volume, cooling to room temperature, filtering to obtain a solid, washing the filter cake with an appropriate amount of tolueneAnd the resulting cake was put into 55 g of isopropyl alcohol while adding 1 g of activated charcoal to a temperature of 60 CAnd the filtrate is cooled to below 10 degrees. The filtrate is filtered and washed with cold isopropanol to obtain methimazole wet product. After vacuum drying, 21.4 g of methimazole is obtained. The yield is 72%. The obtained methimazole color is white crystal with 99.6% HPLC purity and less than 1000 ppb common metal ion content |