Reactive intermediates in the reaction of hydrazinecarbothioamides with 2-(bis(methylthio)methylene)malononitrile and ethyl 2-cyano-3,3-bis(methylthio)acrylate

Aly, Ashraf A.; Hassan, Alaa A.; Mohamed, Nasr K.; El‐Shaieb, Kamal M.; Makhlouf, Maysa M.; Bräse, Stefan; Nieger, Martin

doi:10.1007/s11164-018-3633-4

Cited by 3 publications

(5 citation statements)

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“…In the same manner, bis-spirotriazolethione 187 was synthesized from the reaction of 1,1′-(propane-1,3-diyl)bis(5-bromoindoline-2,3-dione) 186 with 20 in 89% yield (Scheme 51) [80]. Microwave irradiation was used as an efficient method to get good yields with a shorter time than the classical method for the synthesis of 6,6-dimethyl-phenyl-1,2,4,8-tetrazaspiro [4.5]decane-3thiones 193a-e via formation of thiosemicarbazone intermediates 192a-e, which was obtained from the reaction of 3,3-dimethyl-phenylpiperidin-4-ones 191a-e with 20 (Scheme 53) [82]. Aly et al [82] reported that reaction of equal equivalents of both N-substituted hydrazinecarbothioamides 23a,i with 2-(bis(methylthio)methylene)malononitrile (197) in dry ethanol catalyzed by few drops of Et 3 N for 3 h afforded a colorless precipitate of 5-amino-4-cyano-3-(methylthio)-N-phenyl-1H-pyrazole-1-carbothioamide (198) as the major product in 65% yield together with 3,4-disubstituted amino-1H-1,2,4-triazole-5(4H)-thiones 199a,b and pyrazole carbonitrile 200 as minor products (Scheme 55) [82].…”

Section: Synthesis Of Spiro-124-triazolethionesmentioning

confidence: 99%

“…Aly et al [ 82 ] reported that reaction of equal equivalents of both N -substituted hydrazinecarbothioamides 23a , i with 2-(bis(methylthio)methylene)malononitrile ( 197 ) in dry ethanol catalyzed by few drops of Et 3 N for 3 h afforded a colorless precipitate of 5-amino-4-cyano-3-(methylthio)- N -phenyl-1 H -pyrazole-1-carbothioamide ( 198 ) as the major product in 65% yield together with 3,4-disubstituted amino-1 H -1,2,4-triazole-5(4 H )-thiones 199a , b and pyrazole carbonitrile 200 as minor products ( Scheme 55 ) [ 82 ].…”

Section: Synthesis Of 124-triazole-3-thionesmentioning

confidence: 99%

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Chemistry and Biological Activities of 1,2,4-Triazolethiones—Antiviral and Anti-Infective Drugs

et al. 2020

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Mercapto-substituted 1,2,4-triazoles are very interesting compounds as they play an important role in chemopreventive and chemotherapeutic effects on cancer. In recent decades, literature has been enriched with sulfur- and nitrogen-containing heterocycles which are used as a basic nucleus of different heterocyclic compounds with various biological applications in medicine and also occupy a huge part of natural products. Therefore, we shed, herein, more light on the synthesis of this interesting class and its application as a biologically active moiety. They might also be suitable as antiviral and anti-infective drugs.

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Section: Synthesis Of Spiro-124-triazolethionesmentioning

confidence: 99%

Section: Synthesis Of 124-triazole-3-thionesmentioning

confidence: 99%

Chemistry and Biological Activities of 1,2,4-Triazolethiones—Antiviral and Anti-Infective Drugs

et al. 2020

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“…Recently, we have an interest in the preparation of heterocycles of similar structural features [15][16][17][18][19][20][21][22][23]. In addition, we prepared metal complexes of thiosemicarbazones with Cu(I) and Cu(II) and the tridentate and bidentate structures of the paracyclophanyl-thiosemicarbazone-metal complexes were elucidated [24].…”

Section: Introductionmentioning

confidence: 99%

“…Figure16. The 2D and 3D diagrams illustrate the binding mode of 3a interacting with the colchicine binding site of β-tubulin.…”

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New Paracyclophanylthiazoles with Anti-Leukemia Activity: Design, Synthesis, Molecular Docking, and Mechanistic Studies

et al. 2020

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A new series of methyl 2-(2-(4′-[2.2]paracyclophanyl)-hydrazinylidene)-3-substituted-4-oxothiazolidin-5-ylidene)acetates 3a–f were synthesized from the reaction of paracyclophanyl-acylthiosemicarbazides 2a–f with dimethyl acetylenedicarboxylate. Based upon nuclear magnetic resonance (NMR), infrared (IR), and mass spectra (HRMS), the structure of the obtained products was elucidated. X-ray structure analysis was also used as unambiguous tool to elucidate the structure of the products. The target compounds 3a–f were screened against 60 cancer cell lines. They displayed anticancer activity against a leukemia subpanel, namely, RPMI-8226 and SR cell lines. The activity of compound 3a was found as the most cytotoxic potency against 60 cancer cell lines. Consequently, it was selected for further five doses analysis according to National Cancer Institute (NCI) protocol. The cytotoxic effect showed selectivity ratios ranging between 0.63 and 1.28 and between 0.58 and 5.89 at the GI50 and total growth inhibition (TGI) levels, respectively. Accordingly, compound 3a underwent further mechanistic study against the most sensitive leukemia RPMI-8226 and SR cell lines. It showed antiproliferation with IC50 = 1.61 ± 0.04 and 1.11 ± 0.03 µM against RPMI-8226 and SR cell lines, respectively. It also revealed a remarkable tubulin inhibitory activity, compared to colchicine with IC50 = 4.97 µM/mL. Caspase-3, BAX, and Bcl-2 assays for 3a using annexin V-FITC staining revealed significant pro-apoptotic activity. Furthermore, multidrug-resistant leukemia SR cells were used to show better resistance indices (1.285 ng/mL, 1.15-fold) than the reference. Docking studies with β-tubulin indicate that most of the tested compounds illustrated good binding at the colchicine binding site of the enzyme, especially for compound 3a, which made several interactions better than that of the reference colchicine.

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“…rings, for example, pyrazoles, triazole thione, and thiadiazoles, can be obtained via reaction of N-substituted hydrazinecarbothioamides with both 2-bis(methylthio)methylene)malononitrile and ethyl 2-cyano-3,3-bis (methylthio)-acrylate. [19] In light of our general aim to screen compounds of biological and pharmaceutical importance, we designed, synthesized, and screened a large variety of biologically active compounds. [20][21][22][23][24][25][26][27] The total number of people with diabetes has been projected to increase from 171 million in 2000 to 366 million by 2030.…”

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Design and synthesis of hydrazinecarbothioamide sulfones as potential antihyperglycemic agents

Aly

Hassan

Makhlouf

et al. 2021

Archiv der Pharmazie

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New hydrazinecarbothioamides with a phenylsulfonyl group were synthesized and their structures were identified by different spectroscopic data ( 1 H NMR, 13 C NMR, two-dimensional NMR, mass spectrometry, elemental analysis, and single-crystal X-ray analysis). The mechanism describing the formation of the products was also discussed.The antidiabetic activity of the isolated products was investigated histochemically. The synthesized sulfonylalkylthiosemicarbazide exhibited antihyperglycemic activity in streptozotocin-induced diabetic mice. Compounds 5a and 5c significantly lowered the blood glucose level to 103.3 ± 1.8 and 102 ± 3.9 mg/dl, respectively. Also, they caused a significant decrease in malondialdehyde levels and normalized the glutathione levels in streptozotocin-induced diabetic mice, compared with the diabetic group. The results suggest that the synthesized hydrazinocarbothioamides may effectively inhibit the development of oxidative stress in diabetes. K E Y W O R D S4-substituted hydrazinecarbothioamides, antihyperglycemic activity, bis(2-(phenylsulfonyl)ethyl)sulfane, glutathione, malondialdehyde, sulfonylalkylthiosemicarbazide | INTRODUCTIONDue to the significant impact of sulfone compounds in biological applications, the development of new sulfone-containing compounds remains one of the central challenges of organic chemistry. [1,2] There are many sulfones widely reported in the literature with a broad spectrum of biological activities such as anticancer, [3] antimicrobial, [4] antiinflammatory, [5] antiproliferative, [6,7] antimalarial [8] and anti-HIV activities. [9] Catalytic chemoselective addition of amino alcohols to α,βunsaturated sulfonyl derivatives leads to the regioselective formation of amino and hydroxy adducts, depending on different catalysts and reaction conditions. [10,11] N-Substituted hydrazinecarbothioamides are considered as one of the most important classes of compounds containing nitrogen, sulfur, and oxygen used for heterocyclization and formation of different heterocyclic rings such as thiadiazole and thiadiazepine, and from the reaction with several π-deficient compounds. [12][13][14][15] The literature approach was applied to 4-(1-phenyl-1Htetrazole-5-ylsulfonyl)butanenitrile (PTSB), a growth inhibitory compound with a previously unknown mode of action, and the thioredoxin/ thioredoxin reductase system was identified as its target. [16] Another patent showed compounds having CH 2 CH 2 SO 2 Ar functional group as histone deacetylase inhibitors. [17][18] The synthesis of various heterocyclic

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Reactive intermediates in the reaction of hydrazinecarbothioamides with 2-(bis(methylthio)methylene)malononitrile and ethyl 2-cyano-3,3-bis(methylthio)acrylate

Cited by 3 publications

References 26 publications

Chemistry and Biological Activities of 1,2,4-Triazolethiones—Antiviral and Anti-Infective Drugs

Chemistry and Biological Activities of 1,2,4-Triazolethiones—Antiviral and Anti-Infective Drugs

New Paracyclophanylthiazoles with Anti-Leukemia Activity: Design, Synthesis, Molecular Docking, and Mechanistic Studies

Design and synthesis of hydrazinecarbothioamide sulfones as potential antihyperglycemic agents

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