157997-38-1Relevant academic research and scientific papers
Selenium analogues of anti-thyroid drugs
Roy, Gouriprasanna,Mugesh, Govindasamy
, p. 908 - 923 (2008)
The inhibition of lactoperoxidase (LPO)-catalyzed oxidation of ABTS by anti-thyroid drugs and related derivatives is described. The commonly used anti-thyroid agent methimazole (MMI) inhibits the LPO with an IC50 value of 7.0 1.1 M which is much lower than that of the other two anti-thyroid drugs, PTU and MTU. The selenium analogue of methimazole (MSeI) also inhibits LPO with an IC50 value of 16.4 1.5 M, which is about 4-5 times lower than that of PTU and MTU. In contrast to thiones and selones, the S- and Se-protected compounds do not show any noticeable inhibition under identical experimental conditions. While the inhibition of LPO by MMI cannot be reversed by increasing the hydrogen peroxide concentration, the inhibition by MSeI can be completely reversed by increasing the peroxide concentration. Experimental and theoretical studies were performed on a number of selones, which suggest that these compounds exist as selenolates or zwitterions in which the selenium atom carries a large negative charge. The structures of selones were studied in solution by NMR spectroscopy and the 77Se NMR chemical shifts for the selones show large upfield shifts in the signals, confirming the zwitterionic structure of the selones in solution. The thermal isomerization of some S- and Se-substituted methyl and benzyl imidazole derivatives to produce the thermodynamically more stable N-substituted derivatives is described.
Interactions of antithyroid drugs and their analogues with halogens and their biological implications
Roy, Gouriprasanna,Bhabak, Krishna P.,Mugesh, Govindasamy
experimental part, p. 2279 - 2286 (2012/05/05)
The selenium analogue of antithyroid drug methimazole (MSeI) reacts with molecular bromine to produce two different types of novel complexes depending upon the molar ratio of MSeI to Br2 in the reaction medium. Dicationic diselenide complex wit
Antithyroid drugs and their analogues protect against peroxynitritemediated protein tyrosine nitration-a mechanistic study
Bhabak, Krishna P.,Mugesh, Govindasamy
experimental part, p. 1175 - 1185 (2010/06/19)
In this paper, the effect of some commonly used antithyroid drugs and their analogues on peroxynitritemediated nitration of proteins is described. The nitration of tyrosine residues in bovine serum albumin (BSA) and cytochrome c was studied by Western blot analysis. These studies reveal that the antithyroid drugs methimazole (MMI), 6-n-propyl-2-thiouracil (PTU), and 6-methyl-2- thiouracil (MTU), which contain thione moieties, significantly reduce the tyrosine nitration of both BSA and cytochrome c. While MMI exhibits good peroxynitrite (PN) scavenging activity, the thiouracil com-pounds PTU and MTU are slightly less effective than MMI. The S- and Semethylated compounds show a weak inhibitory effect in the nitration of tyrosine, indicating that the presence of a thione or selone moiety is important for an efficient inhibition. Similarly, the replacement of N-H moiety in MMI by N-methyl or N-m-methoxybenzyl substituents dramatically reduces the antioxidant activity of the parent com-pound. Theoretical studies indicate that the substitution of N-H moiety by NMe significantly increases the energy required for the oxidation of sulfur center by PN. However, such substitution in the selenium analogue of MMI increases the activity of parent compound. This is due to the facile oxidation of the selone moiety to the corresponding selenenic and seleninic acids. Unlike N,N'-disubstituted thiones, the corresponding selones efficiently scavenge PN, as they predominantly exist in their zwitterionic forms in which the selenium atom carries a large negative charge.
Synthesis and structural characterization of 1-mesityl-1,3-dihydro- imidazole-2-selone and bis(1-mesitylimidazol-2-yl)diselenide: Experimental evidence that the selone is more stable than the selenol tautomer
Landry, Victoria K.,Minoura, Mao,Pang, Keliang,Buccella, Daniela,Kelly, Bryte V.,Parkin, Gerard
, p. 12490 - 12497 (2007/10/03)
1-Mesityl-1,3-dihydro-imidazole-2-selone, (seimMes)H, may be obtained from 1-mesitylimidazole via (i) deprotonation with BunLi, (ii) treatment with elemental selenium, and (iii) addition of HCl(aq). Structural characterization of (se
Anti-thyroid drugs and thyroid hormone synthesis: Effect of methimazole derivatives on peroxidase-catalyzed reactions
Roy, Gouriprasanna,Mugesh
, p. 15207 - 15217 (2007/10/03)
Syntheses and characterization of the selenium analogue (MSeI) of anti-thyroid drug methimazole and a series of organoselenium compounds bearing N-methylimidazole pharmacophore are described. In contrast to the sulfur compound that exists predominantly in its thione form, the selenium analogue exists in a selenol form, which spontaneously oxidizes in air to produce the corresponding diselenide. The reduction of the diselenide by GSH or NaBH 4 affords the biologically active selenol, which effectively inhibits the lactoperoxidase (LPO) activity in vitro. The monoselenides having N-methylimidazole moiety are found to be much less active than the selenol, suggesting that the presence of a selenol moiety is important for the LPO inhibition. The kinetic and mechanistic studies reveal that MSeI inhibits the LPO activity by reducing the H2O2, providing a novel method to reversibly inhibit the enzyme. Although MSeI strongly inhibits LPO, the enzyme's activity can be completely recovered by increasing the H 2O2 concentration. On the other hand, the inhibition by methimazole (MMI), the sulfur analogue, cannot be reversed by increasing the H2O2 concentration, leading to a complete inactivation of the enzyme. The reversible inhibition of LPO by some of the selenium derivatives is correlated with their glutathione peroxidase (GPx) activity, and the high GPx activity of the selenium compounds as compared with their sulfur analogues suggests that the selenium derivatives may protect the thyroid gland from oxidative damage.
