- S-methylation of diethyldithiocarbamic acid in rat liver microsomes
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1. Human hepatic thiol methyltransferase (TMT) is a microsomal enzyme known to catalyse the in vitro S-methylation of diethyldithiocarbamic acid (DDC) to form diethyldithiocarbamic acid methyl ester (methyl DDC). In vivo data are needed to investigate further the biotransformation of DDC to methyl DDC. Thus, we have characterized the in vitro conversion of DDC to methyl DDC using rat liver microsomes with the ultimate goal of establishing an animal model. 2. Formation of methyl DDC in rat liver microsomes was confirmed by hplc analysis. 3. Rat liver microsomes catalysed methylation of DDC with low and high K(m)'s of 5 ± 6 and 260 ± 80 μM respectively and with corresponding V(max)'s of 0.09 ± 0.05 and 0.59 ± 0.04 nmol/min/mg protein. 4. Rat liver TMT activity was maximally inhibited by 57 ± 6% by 1000 μM 2,3-dichloro-α-methylbenzylamine (DCMB), whereas human TMT was completely inhibited. The concentration of half maximal inhibition of rat TMT for DCMB was 2 μM. 5. Incomplete inhibition of rat TMT activity by DCMB suggests a possible alternative pathway of methylation.
- Lill,Mays,Lipsky
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- An efficient synthesis of dithiocarbamates under ultrasound irradiation in water
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Multicomponent reactions with ultrasonic activation have been used as a simple, rapid, atom economic, and green method for the synthesis of dithiocarbamate derivatives in water. The one-pot, three-component condensation of primary and secondary amines with carbon disulfide and unsaturated carbonyl compounds or alkyl halides under ultrasonic irradiation was developed as a green and fast protocol for the rapid high-yielding preparation of dithio-carbamates in water.
- Azizi, Najmadin,Gholibeglo, Elahm,Nayeri, Sanaz Dehghan
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experimental part
p. 1171 - 1174
(2012/09/25)
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- Exploring the structural requirements for inhibition of the ubiquitin E3 ligase breast cancer associated protein 2 (BCA2) as a treatment for breast cancer
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The zinc-ejecting aldehyde dehydrogenase (ALDH) inhibitory drug disulfiram (DSF) was found to be a breast cancer-associated protein 2 (BCA2) inhibitor with potent antitumor activity. We herein describe our work in the synthesis and evaluation of new series of zinc-affinic molecules to explore the structural requirements for selective BCA2-inhibitory antitumor activity. An N(C - S)S - S motif was found to be required, based on selective activity in BCA2-expressing breast cancer cell lines and against recombinant BCA2 protein. Notably, the DSF analogs (3a and 3c) and dithio(peroxo)thioate compounds (5d and 5f) were found to have potent activity (submicromolar IC50) in BCA2 positive MCF-7 and T47D cells but were inactive (IC50 > 10 μM) in BCA2 negative MDA-MB-231 breast cancer cells and the normal breast epithelial cell line MCF10A. Testing in the isogenic BCA2 +ve MDA-MB-231/ER cell line restored antitumor activity for compounds that were inactive in the BCA2 -ve MDA-MB-231 cell line. In contrast, structurally related dithiocarbamates and benzisothiazolones (lacking the disulfide bond) were all inactive. Compounds 5d and 5f were additionally found to lack ALDH-inhibitory activity, suggestive of selective E3 ligase-inhibitory activity and worthy of further development.
- Brahemi, Ghali,Kona, Fathima R.,Fiasella, Annalisa,Buac, Daniela,Soukupová, Jitka,Brancale, Andrea,Burger, Angelika M.,Westwell, Andrew D.
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supporting information; experimental part
p. 2757 - 2765
(2010/08/20)
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- Bis(dialkylaminethiocarbonyl)disulfides as potent and selective monoglyceride lipase inhibitors
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Monoglyceride lipase (MGL) inhibition may offer an approach in treating diseases in which higher 2-arachidonoyglycerol activity would be beneficial. We report here the synthesis and pharmacological evaluation of bis(dialkylaminethiocarbonyl)disulfide derivatives as irreversible MGL inhibitors. Inhibition occurs through interactions with MGL C208 and C242 residues, and these derivatives exhibit high inhibition selectivity over fatty acid amide hydrolase, another endocannabinoid-hydrolyzing enzyme. 2009 American Chemical Society.
- Kapanda, Coco N.,Muccioli, Giulio G.,Labar, Geoffray,Poupaert, Jacques H.,Lambert, Didier M.
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experimental part
p. 7310 - 7314
(2010/07/14)
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- Straightforward and highly efficient catalyst-free one-pot synthesis of dithiocarbamates under solvent-free conditions
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A highly efficient and simple synthesis of dithiocarbamates is possible based on the one-pot reaction of amines, CS2, and alkyl halides without using a catalyst under solvent-free conditions. The mild reaction conditions, high yields, and broad scope of the reaction illustrate the good synthetic utility of this method. The reaction is a highly atom-economic process for production of S-alkyl thiocarbamates and successfully can be used in high quantities in the pharmaceutical or agrochemical industries.
- Azizi, Najmedin,Aryanasab, Fezzeh,Saidi, Mohammad R.
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p. 5275 - 5277
(2007/10/03)
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- Accelerated degradation of methyl iodide by agrochemicals
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The fumigant methyl iodide (Mel, iodomethane) is considered a promising alternative to methyl bromide (MeBr) for soil-borne pest control in high-cash-value crops. However, the high vapor pressure of Mel results in emissions of a significant proportion of the applied mass into the ambient air, and this may lead to pollution of the environment. Integrating the application of certain agrochemicals with soil fumigation provides a novel approach to reduce excessive fumigant. emissions. This study investigated the potential for several agrochemicals that are commonly used in farming operations, including fertilizers and nitrification inhibitors, to transform Mel in aqueous solution. The pseudo-first-order hydrolysis half-life (t1/2) of Mel was ~ 108 d, while the transformation of Mel in aqueous solutions containing selected agrochemicals was more rapid, with t1/2 1/2 1/2 of Mel was 1/2 > 300 h).
- Zheng, Wei,Papiernik, Sharon K.,Guo, Mingxin,Yates, Scott R.
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p. 673 - 679
(2007/10/03)
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- Pesticidal compositions containing phosphoric esters and divalent sulphur compounds
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Pesticidal composition comprising: a pesticidal, phosphoric ester the molecule of which has at least one alkyl group of 1 to 3 carbon atoms, 0.05 to 10% of an agent stabilizing the said ester against decomposition by protonisation, together with adjuvants characterized in that the stabilizing agent comprises at least one sulphur compound containing per molecule at least one divalent sulphur atom of which one valence is bonded to an atom chosen from sulphur, carbon, nitrogen, hydrogen, and metals capable of giving a salt, the other valence being bonded to an atom chosen from hydrogen, the carbon atom already noted, a second carbon atom, the nitrogen atom already noted, a second nitrogen atom, the metal atom already noted in the case of a metal of valence greater than one, a second atom of metal and oxygen when the first valence is not attached to an atom of hydrogen, the proportion of sulphur calculated with reference to the weight of the sulphur compound being between 5 and 99%. Process for stabilizing a phosphoric ester of which the molecule possesses at least one alkyl group containing 1 to 3 carbon atoms characterized in that there is added to the phosphoric ester or to a mixture which contains it, 0.05 to 10% calculated on the weight of the phosphoric acid ester of an agent capable of stabilizing the said phosphoric ester against protonisation and comprising at least one sulphur compound such as that defined thereupon.
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