- Discovery and optimization of novel dual dithiocarbamates as potent anticancer agents
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A series of dual dithiocarbamates were synthesized and evaluated for their in-vitro anticancer activities on human non-small cell lung cancer cell line H460. Nine compounds exhibited significant antiproliferative activities with IC50 less than 1 μM. Among them, compound 14m showed the highest inhibitory activity against H460 cell and inhibited the growth of nine types of tumor cells with IC50 values less than 1 μM. It also achieved IC50 of 54 nM and 23 nM against HepG2 and MCF-7 cell lines, respectively. Preliminary structure-activity relationship study indicated that: a) when the methyl group (region A) is substituted with benzene rings, ortho substitution on the benzene ring is favored for activity; b) substitution with heterocyclic structures at region A exhibited greater impact on the anti-tumor activity of compounds, in which pyridine ring, thiazole ring, coumarin and benzo[b]thiophene are favored and quinoline ring is the most favored; c) substitution with different amines (region B) also showed marked effect on the activity of compounds and dimethylamine and morpholine are preferred to other tested amines.
- Li, Ri-Dong,Wang, Hui-Ling,Li, Ying-Bo,Wang, Zhong-Qing,Wang, Xin,Wang, Yi-Tao,Ge, Ze-Mei,Li, Run-Tao
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p. 381 - 391
(2015/03/04)
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- Synthesis and antitumor activity of tetrahydrocarbazole hybridized with dithioate derivatives
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The present study reported the synthesis of tetrahydrocarbazoles hybridized with dithioate derivatives. Three series were synthesized namely alkyl dithiocarbonates (4a-d), heterocyclic dithiocarbamates (6a-g) and dialkyl dithiocarbamate (7). The synthesized compounds were tested in vitro on human breast adenocarcinoma cell line (MCF7) and the human colon tumor cell line (HCT116). Most of the synthesized compounds exploited potent antitumor activity, especially compound 6f [4-chlorophenylpiperazine derivative], which showed cytotoxic activity against MCF7 superior to doxorubicin with IC50 value of 7.24 nM/mL.
- El-Nassan, Hala Bakr
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p. 308 - 315
(2015/04/14)
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- A manufacturing method of manufacturing method biscarbodithioate aq. amines and amine of the solid biscarbodithioate
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PROBLEM TO BE SOLVED: To solve such a problem that the conventional method for obtaining a solid amine carbodithioate salt is not efficient, and in particular, when an amine carbodithioate salt has high solubility, it has been difficult to efficiently obtain the solid amine carbodithioate salt.SOLUTION: In a method for producing an amine carbodithioate salt by mixing an amine, carbon disulfide, and a metal hydroxide in an aqueous solution and making them react with one another, the solid amine carbodithioate salt is efficiently obtained by making 1.3 times equivalent or more of the metal hydroxide with respect to the amino group of the amine to react with carbon disulfide coexist therewith. Moreover, an aqueous solution of the amine carbodithioate salt with high concentration is simultaneously produced by further mixing the amine, carbon disulfide, and the metal hydroxide with the aqueous solution of the amine carbodithioate salt from which the solid amine carbodithioate salt has been separated and making them react with one another.
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Paragraph 0036
(2017/06/29)
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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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- Synthesis and in vitro antifungal activity of some N,N-disubstituted dithiocarbamic acid esters derived from 2-methylquinazolinones
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A series of 2-[(N,N-disubstituted thiocarbamoylthio)methyl]quinazolinones 9a-g; 10a; 10d; 11a-d and 12a were synthesized and evaluated for potential antifungal activity against a variety of fungal species. The synthesis of the target compounds was achieved by reaction of the potassium salts of disubstituted dithiocarbamic acids 8a-g and the respective 2-bromomethyl-4(3H)-quinazolinone 4 or 3-aryl-2- chloromethyl-4(3H)-quinazolinones 5-7. The dithiocarbamic acid derivatives were synthesized in a one step reaction from the appropriate amine, alcoholic potassium hydroxide solution and carbon disulfide. TLC and elemental analyses ascertained the purity of the synthesized compounds and their structures were confirmed by IR and 1H-NMR spectroscopy, 2-Methyl-4(3H)-quinazolinone 2, the precursor of the 2-bromomethyl intermediate 4, was selected as representative example for detailed spectroscopic investigations, including 300 MHz 1H- and 13CNMR in addition to HH COSY; APT and 1H13C HETCOR spectra, with the aim of establishing correct assignment of the spectral data of related compounds. The synthesized disubstituted dithiocarbamates 9a-g; 10a,d; 11a-d and 12a as well as tolnaftate and clotrimazole, as reference drugs, were tested in vitro at 2 and 5% concentrations against 23 pathogenic fungi. The study revealed that compound 9a exhibited broad spectrum inhibitory activity that is superior or comparable to that of the reference drugs against the tested fungal isolates. Selective fungistatic activity against Candida species was elicited by compound 9e and against Microsporum species as well as Trichophyton mentagrophytes was also observed for compound 9g. As a general pattern it might be postulated that some of the synthesized dithiocarbamate derivatives showed broad spectrum antifungal activity as compared with tolnaftate, the clinically used thiocarbamate compound, and also exhibited comparable activity to clotrimazole against Candida species and F. Solani.
- Farghaly,Moharram
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p. 280 - 289
(2007/10/03)
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- Synthesis and pharmacology of new dithiocarbamic acid esters derived from phenothiazine and diphenylamine
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2-Methylthio-10-[N,N-disubstituted-thiocarbamoylthio)acetyl]- phenothiazines (4a-g) and N-(3-methylthiophenyl)-N-[(N,N-disubstituted- thiocarbamoylthio)acetyl]phenylamines (5a-g) were synthesized by subsequent treatment of 2-methylthio-10-chloroacetylphenothiazines (1) and N-(3- methylthiophenyl)-N-chloroacetylphenylamine (2) with potassium salts of N,N- disubstituted dithiocarbamic acid derivatives (3a-i). The structures of the compounds were determined by analytical and spectral (IR, 1H NMR, 13C NMR, EIMS) methods. The antihistaminic and anticholinergic activities of 4a, 4c, 4e-g, 5a-c 5e, and 5g were evaluated in comparison with H1-receptor antagonist mepyramine and nonselective cholinergic antagonist atropine. In the first series of experiments, the cumulative concentration-response curves to histamine (10-8-10-4 M) and acetylcholine (10-8-10-4 M) were constructed in separate fundus strips. The test compounds exhibited marked antihistaminic activity at 10-6 M concentration but compounds did not influence acetylcholine induced contractions. Concentration-related experiments carried out on 4g and 5g revealed that a moderate antihistaminic activity was present at 10-7 M concentration of the compounds and became strong at higher concentrations. In the second series of experiments, the cumulative concentration-response curve to histamine (10-9-10-4 M) was constructed in guinea-pig ileum segments. Maximal responses were obtained by 10-6-3 x 10-6 M concentrations of histamine in ileum segments. Similar inhibitions of histamine contractions were also obtained with the test compounds. Their inhibitory effectiveness was evaluated by comparing the pA2 values.
- Karali, Nilguen,Apak, Idil,Oezkirimli, Sumru,Guersoy, Aysel,Dogan, Soenmez Uydes,Eraslan, Aylin,Oezdemir, Osman
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p. 422 - 426
(2007/10/03)
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- Synthesis, characterization and in-vitro antifungal evaluation of some dithiocarbamic acid derivatives
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Some new N, N-disubstituted dithiocarbamates derived from α-acetonaphthone and their precursors, potassium salts of dithiocarbamic acid, were prepared and evaluated for antifungal activity. Synthesis involved the reaction of α-chloro-2-acetonaphthone or α-chloro-4-methoxy-1-acetonaphthone with the potassium salts of N, N-disubstituted dithiocarbamic acid (5a-g). Compounds 5a-g were readily produced by reaction of equivalent amounts of the appropriate secondary amine, potassium hydroxide and carbon disulphide. The purity of the final derivatives, N, N-disubstituted dithiocarbamates 6a-g and 7a-g, was determined elemental analyses and TLC, and assignment of structures was confirmed by IR, 1H NMR, 13C NMR and MS. Preliminary evaluation of the antifungal activity of derivatives 5a-g, 6a-g and 7a-g was determined in-vitro at a 2.5 or 5.0% concentration against different fungal species using tolnaftate as a reference drug. The potassium salts 5a-g were the most potent derivatives of the tested series. Compounds 5a-g showed significant broad spectrum antifungal activity. Combination of the dithiocarbamate with acetonaphthonyl moiety, represented by the 6a-g and 7a-g series, resulted in a decrease in or complete loss of antifungal activity in certain derivatives. Compounds derived from 4-methoxy-1-acetonaphthone (7a-g) were generally superior to their 4-nonsubstituted congeners (6a-g). The morpholino dithiocarbamate derivative 7e was equipotent or superior to the reference drug against the tested dermatophytes species and Rhodotorula rubra at a 5% concentration. In addition, 7e exhibited inhibitory activity against Chrysosporium tropicum, Emericella nidulans, Penicillium aurantiogriseum and Aspergillus sydowii. Some derivatives of both series showed selective activity against certain fungi, (e.g. 6f against Phoma glomerata and Scopulariopsis acremonium; 6g against Emericella nidulans and Phoma glomerata; 7c against Geotrichum candidum and Mucor circinelloides; 7d against Geotrichum candidum, Penicillium aurantiogriseum and Rodotorula rubra and 7f against Mucor circinelloides).
- Mahfouz, Nadia M.,Moharram, Ahmad M.
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p. 315 - 322
(2007/10/03)
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- Synthesis characterization and biological evaluation of 2-methyl-3-(N-substituted thiocarbamoylthio)acetamido-4(3H)-quinazolinones
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Reaction of 3-chloroacetamido-2-methyl-4(3H)-quinazolinones (1 and 2) with appropriately substituted potassium dithiocarbamates (3) furnished 2-methyl-3-(N-substituted thiocarbamoylthio)acetamido-4(3H)-quinazolinones (4 and 5) which exist as isomeric mixtures. The structures of 4 and 5 were determined by analytical and spectral (IR, 1H-NMR, EIMS, CIMS(CH4 or NH3)) methods. All the compounds except for 4g and 5g were tested for antimicrobial activity against some bacteria und fungi. Only 4b and 4c were found active against Staphylococcus aureus (MIC 100 μg/ml). 4d, 4e, 4g, 4h, 5a-f and 5h were also evaluated for anticonvulsant activity but were found inactive.
- Capan,Ergenc,Buyuktimkin,Yulug
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p. 243 - 250
(2007/10/02)
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- Secondary Bonding. Part 15. Influence of Lone Pairs on Co-ordination: Comparison of Diphenyl-Tin(IV) and -Tellurium(IV) Carboxylates and Dithiocarbamates
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Seven complexes of general type Ph2MX2 with X = carboxylate or dithiocarbamate have been prepared and their molecular structures determined (M = Sn, X = O2CMe, O2CCH2Cl, or S2CNEt2; M = Te, X = O2CCCl3, S2CNEt2, S2CNEtPh, or S2CNPh2).All but one show unsymmetrical bidentate co-ordination by the carboxylate or dithiocarbamate ligands; the tellurium complexes show substantially greater differences between the longer and shorter M-O or M-S distances.The presence of the lone pair transforms the co-ordination geometry from approximately tetrahedral (M = Sn) to pseudo-trigonal bipyramidal (M = Te).Replacing carboxylates by dithiocarbamate has a modest effect when M = Te, but in the tin compound the sulfur ligand co-ordination is almost symmetrical.This contrasts with the unsymmetrical bonding in Me2Sn(S2CNEt2)2.
- Alcock, Nathaniel W.,Culver, Jane,Roe, S. Mark
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p. 1477 - 1484
(2007/10/02)
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