5397-03-5Relevant articles and documents
Synthesis, characterization, antiparasitic and cytotoxic evaluation of thioureas conjugated to polyamine scaffolds
Stringer, Tameryn,Taylor, Dale,De Kock, Carmen,Guzgay, Hajira,Au, Aaron,An, Seung Hwan,Sanchez, Benjamin,O'Connor, Raquel,Patel, Neal,Land, Kirkwood M.,Smith, Peter J.,Hendricks, Denver T.,Egan, Timothy J.,Smith, Gregory S.
, p. 90 - 98 (2013)
A series of mono- and multimeric 4-amino-7-chloroquinoline and ferrocenyl thioureas have been prepared by the reaction of a 7-chloroquinoline methyl ester and a ferrocenylimine methyl ester with various amines. These compounds were characterized using standard spectroscopic and analytical techniques. The compounds were evaluated against the NF54 (CQ-sensitive) and Dd2 (CQ-resistant) strains of Plasmodiumfalciparum. The quinoline compounds show enhanced activity compared to the ferrocene compounds against this parasite. Compound 5 displays the most promising activity against the NF54 strain. Compounds 5 and 6 are effective at inhibiting β-hematin formation perhaps due to an increased number of quinoline moieties. The trimeric (12) and tetrameric (13) ferrocenyl compounds also inhibit β-hematin formation, albeit to a lesser degree compared to the quinoline thioureas. The compounds were also screened against the G3 strain of Trichomonasvaginalis and here the ferrocene-containing compounds show a slightly higher parasite growth inhibition compared to the quinoline thioureas. The quinoline compounds were also found to be more cytotoxic compared to the ferrocenyl compounds. Compound 6 displays good cytotoxicity against WHCO1 oesophageal cancer cells.
Coordinated dissociative proton transfers of external proton and thiocarbamide hydrogen: MS experimental and theoretical studies on the fragmentation of protonated S-methyl benzenylmethylenehydrazine dithiocarboxylate in gas phase
Jiang, Kezhi,Bian, Gaofeng,Hu, Nan,Pan, Yuanjiang,Lai, Guoqiao
, p. 17 - 23 (2010)
The dissociation chemistry of the protonated S-methyl benzenylmethylenehydrazine dithiocarboxylate, PhCH{double bond, long}N{single bond}NHC({double bond, long}S)SCH3, has been investigated by collision-induced dissociation (CID) mass spectrometry experiments in combination with density functional theory (DFT) calculations. Eliminations of H2S, CH3SH and (NSC)SCH3 were the three fragmentation reactions observed in the tandem mass spectra, witnessed by the MS/MS analysis of native 34S-isotopic ion and the D-labeling CID-MS experiment. Of the three fragmentations, both the added proton and the internal thiocarbamide hydrogen shift to the fragment ion (m/z 106) in the dissociation of losing (NSC)SCH3, while both of them shift to the neutral fragment H2S to generate the minor product ion at m/z 177. In the case of the feasible fragmentation process of CH3SH elimination, one of the proton/the thiocarbamide hydrogen migrates to the fragment ion at m/z 163, and the other migrates to the neutral specie. Calculated results show that thiocarbamide sulfur (S5) is the most thermodynamically favored position for protonation. The mechanisms of these reactions were postulated according to the theoretical results, and the reaction energy profiles were also constructed. These results indicated that fragmentation of the protonated molecule was viewed as a result of the coordinated migration of both the external proton and the thiocarbamide hydrogen.
Copper-Binding Small Molecule Induces Oxidative Stress and Cell-Cycle Arrest in Glioblastoma-Patient-Derived Cells
Shimada, Kenichi,Reznik, Eduard,Stokes, Michael E.,Krishnamoorthy, Lakshmi,Bos, Pieter H.,Song, Yuyu,Quartararo, Christine E.,Pagano, Nen C.,Carpizo, Darren R.,deCarvalho, Ana C.,Lo, Donald C.,Stockwell, Brent R.
, p. 585 - 7,594 (2018)
Transition metals are essential, but deregulation of their metabolism causes toxicity. Here, we report that the compound NSC319726 binds copper to induce oxidative stress and arrest glioblastoma-patient-derived cells at picomolar concentrations. Pharmacogenomic analysis suggested that NSC319726 and 65 other structural analogs exhibit lethality through metal binding. Although NSC319726 has been reported to function as a zinc ionophore, we report here that this compound binds to copper to arrest cell growth. We generated and validated pharmacogenomic predictions: copper toxicity was substantially inhibited by hypoxia, through an hypoxia-inducible-factor-1α-dependent pathway; copper-bound NSC319726 induced the generation of reactive oxygen species and depletion of deoxyribosyl purines, resulting in cell-cycle arrest. These results suggest that metal-induced DNA damage may be a consequence of exposure to some xenobiotics, therapeutic agents, as well as other causes of copper dysregulation, and reveal a potent mechanism for targeting glioblastomas. Shimada et al. report that the compound NSC319726 arrests glioblastoma-patient-derived cells at picomolar concentrations. The compound binds to copper, generates ROS using ambient oxygen, and depletes nucleotide pools. This represents a new strategy for potently blocking the growth of glioblastoma.
Synthetic method 2 -methylsulfonyl -5 - trifluoromethyl -1 , 3, 4 - thiadiazole
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Paragraph 0011, (2021/10/20)
The invention belongs to the technical field of medical intermediates, and particularly relates to a synthetic method 2 -methylsulfonyl -5 - trifluoromethyl -1 , 3, 4 - thiadiazole. To the invention, hydrazine hydrate and carbon disulfide are subjected to addition reaction, and then under basic conditions, dimethyl sulfate is replaced to obtain the intermediate material A, and the intermediate material A is obtained. The intermediate material B is obtained by reacting the intermediate material B with hydrogen peroxide to obtain 2 - methylsulfonyl -5 - trifluoromethyl -1 , 3, 4 - thiadiazole, the operation is simple, the operation is easy, and the yield is high.
CHEMICAL ACTIVATORS OF NICOTINAMIDE MONONUCLEOTIDE ADENLYLY TRANSFERASE 2 (NMNAT2) AND USES THEREOF
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Page/Page column 23; 34-35, (2020/06/22)
The present application relates to novel semicarbazones and thiosemicarbazones, to processes for preparing them, to pharmaceutical preparations comprising them, to the use of the novel semicarbazones and thiosemicarbazones for treatment and/or prophylaxis of diseases and to the use thereof for production of a medicament for treatment and/or prophylaxis of diseases, especially of neurodegeneration and age-associated diseases or conditions associated with NAD loss. The present application also provides a method for high throughput screening of NMNAT2 activators.
Fluconazole analogues with metal-binding motifs impact metal-dependent processes and demonstrate antifungal activity in Candida albicans
Franz, Katherine J.,Hunsaker, Elizabeth W.,McAuliffe, Katherine J.
, (2020/06/26)
Abstract: Azole antifungals are an important class of antifungal drugs due to their low cost, ability to be administered orally, and broad-spectrum activity. However, their widespread and long-term use have given rise to adaptation mechanisms that render these compounds less effective against common fungal pathogens, including Candida albicans. New antifungals are desperately needed as drug-resistant strains become more prevalent. We recently showed that copper supplementation potentiates the activity of the azole antifungal fluconazole against the opportunistic fungal pathogen C. albicans. Here, we report eight new azole analogues derived from fluconazole in which one triazole group has been replaced with a metal-binding group, a strategy designed to enhance potentiation of azole antifungal activity by copper. The bioactivity of all eight compounds was tested and compared to that of fluconazole. Three of the analogues showed activity against C. albicans and two had lower levels of trailing growth. One compound, Flu-TSCZ, was found to impact the levels, speciation, and bioavailability of cellular metals. Graphic abstract: [Figure not available: see fulltext.]
