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Reduction Products (reduction + products)
Selected AbstractsSynthesis of 1,4-Diazepin-5-ones under Microwave Irradiation and Their Reduction Products.CHEMINFORM, Issue 29 2007Nicolas Wlodarczyk Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF. [source] Zinc diethyldithiocarbamate allergenicity: potential haptenation mechanismsCONTACT DERMATITIS, Issue 2 2008Itai Chipinda Background:, Zinc diethyldithiocarbamate (ZDEC) and its disulfide, tetraethylthiuram disulfide (TETD), are rubber accelerators and contact allergens that cross-react in some individuals. Objective:, This study explored potential protein haptenation mechanisms of ZDEC and its oxidation products. Methods:, ZDEC oxidation/reduction products and sites of protein binding were assessed using high-performance liquid chromatography and mass spectrometry. The murine local lymph node assay (LLNA) was employed to probe haptenation mechanisms of ZDEC by examining its allergenicity along with its oxidation products and through elimination of oxidation and chelation mechanisms by substituting cobalt for zinc [cobalt (II) dithiocarbamate, CoDEC]. Results:, Oxidation of ZDEC by hypochlorous acid (bleach, HOCl), iodine, or hydrogen peroxide resulted in production of TETD, tetraethylthiocarbamoyl disulfide, and tetraethyldicarbamoyl disulfide (TEDCD). Albumin thiols reduced TETD with subsequent mixed disulfide formation/haptenation. ZDEC directly chelated the copper ion on the active site of the superoxide dismutase, whereas CoDEC did not bind to Cu proteins or form mixed disulfides with free thiols. ZDEC, sodium diethyldithiocarbamate, TEDCD, and TETD were all positive in the LLNA except CoDEC, which was non-allergenic. Conclusion:, The thiol is the critical functional group in ZDEC's allergenicity, and haptenation is predominantly through chelation of metalloproteins and formation of mixed disulfides. [source] An aminoisoflavone , salicyloylindole ring transformationJOURNAL OF HETEROCYCLIC CHEMISTRY, Issue 3 2004Werner Löwe A series of 2,-nitroisoflavones 8,10, 15, 22, 27 and 28 was prepared via the (2-nitro-phenyl)-acetic acids 1, 13, 19 and 25. In order to obtain the corresponding 2,-aminoisoflavones the reduction of 8,10, 15, 22, 27 and 28 was undertaken. Surprisingly, new 3-salicyloylindoles instead of the expected 2,-aminoisoflavones were the main reduction products. In the following paper the preparation of the 2,-nitroisoflavones 8,10, 15, 22, 27 and 28 as well as the reduction experiments obtaining the 2,-aminoisoflavones 33 and 35 and the 3-salicyloylindoles 29,32, 34 and 36 will be described. Furthermore, a possible mechanism responsible for the formation of the 3-salicyloylindoles from 2,-nitroisoflavones under reductive conditions will be discussed. [source] Facile Oxidation of Leucomethylene Blue and Dihydroflavins by Artemisinins: Relationship with Flavoenzyme Function and Antimalarial Mechanism of ActionCHEMMEDCHEM, Issue 8 2010Richard Abstract The antimalarial drug methylene blue (MB) affects the redox behaviour of parasite flavin-dependent disulfide reductases such as glutathione reductase (GR) that control oxidative stress in the malaria parasite. The reduced flavin adenine dinucleotide cofactor FADH2 initiates reduction to leucomethylene blue (LMB), which is oxidised by oxygen to generate reactive oxygen species (ROS) and MB. MB then acts as a subversive substrate for NADPH normally required to regenerate FADH2 for enzyme function. The synergism between MB and the peroxidic antimalarial artemisinin derivative artesunate suggests that artemisinins have a complementary mode of action. We find that artemisinins are transformed by LMB generated from MB and ascorbic acid (AA) or N -benzyldihydronicotinamide (BNAH) in,situ in aqueous buffer at physiological pH into single electron transfer (SET) rearrangement products or two-electron reduction products, the latter of which dominates with BNAH. Neither AA nor BNAH alone affects the artemisinins. The AA,MB SET reactions are enhanced under aerobic conditions, and the major products obtained here are structurally closely related to one such product already reported to form in an intracellular medium. A ketyl arising via SET with the artemisinin is invoked to explain their formation. Dihydroflavins generated from riboflavin (RF) and FAD by pretreatment with sodium dithionite are rapidly oxidised by artemisinin to the parent flavins. When catalytic amounts of RF, FAD, and other flavins are reduced in,situ by excess BNAH or NAD(P)H in the presence of the artemisinins in the aqueous buffer, they are rapidly oxidised to the parent flavins with concomitant formation of two-electron reduction products from the artemisinins; regeneration of the reduced flavin by excess reductant maintains a catalytic cycle until the artemisinin is consumed. In preliminary experiments, we show that NADPH consumption in yeast GR with redox behaviour similar to that of parasite GR is enhanced by artemisinins, especially under aerobic conditions. Recombinant human GR is not affected. Artemisinins thus may act as antimalarial drugs by perturbing the redox balance within the malaria parasite, both by oxidising FADH2 in parasite GR or other parasite flavoenzymes, and by initiating autoxidation of the dihydroflavin by oxygen with generation of ROS. Reduction of the artemisinin is proposed to occur via hydride transfer from LMB or the dihydroflavin to O1 of the peroxide. This hitherto unrecorded reactivity profile conforms with known structure,activity relationships of artemisinins, is consistent with their known ability to generate ROS in,vivo, and explains the synergism between artemisinins and redox-active antimalarial drugs such as MB and doxorubicin. As the artemisinins appear to be relatively inert towards human GR, a putative model that accounts for the selective potency of artemisinins towards the malaria parasite also becomes apparent. Decisively, ferrous iron or carbon-centered free radicals cannot be involved, and the reactivity described herein reconciles disparate observations that are incompatible with the ferrous iron,carbon radical hypothesis for antimalarial mechanism of action. Finally, the urgent enquiry into the emerging resistance of the malaria parasite to artemisinins may now in one part address the possibilities either of structural changes taking place in parasite flavoenzymes that render the flavin cofactor less accessible to artemisinins or of an enhancement in the ability to use intra-erythrocytic human disulfide reductases required for maintenance of parasite redox balance. [source] Demonstrating the clinical and cost effectiveness of adhesion reduction strategiesCOLORECTAL DISEASE, Issue 5 2002M. S. Wilson Abstract Objective To examine the feasibility of conducting Randomized Controlled Trials (RCT) in lower abdominal surgery to demonstrate a reduction in adhesion-related admissions following use of an adhesion reduction product, and to model the cost effectiveness of such products. Methods The number of patients in each limb of a RCT comparing an adhesion reduction product to a control has been estimated based on 25% and 50% reductions in adhesion-related readmissions one year after surgery, for P = 0.05 at a power of 80% and P = 0.01 at a power of 90%. A cost effectiveness model based on the Surgical and Clinical Adhesions Research Group (SCAR) database has been developed which calculates the percentage reduction in readmissions required of an adhesion reduction product to return the cost of investment. It also estimates the cumulative costs of adhesion-related readmissions for lower abdominal surgery and the cost savings associated with an adhesion reduction policy using a low or high cost product. Results 7.2% of patients undergoing lower abdominal surgery will readmit due to adhesions in the first year after surgery. To demonstrate a 25% reduction in readmissions one year after surgery, it is calculated that a RCT would require between 5686 (P = 0.05, power = 80%) and 7766 (P = 0.01, power = 90%) lower abdominal surgery patients followed-up for one year. A cost effectiveness analysis demonstrates that routine use of adhesion reduction products costing £50 per patient will payback the cost of such investment if they reduce adhesion-related readmissions by 16% after 3 years. A product costing £200 will need to offer a 64.1% reduction in readmissions after 3 years. For the estimated 158 000 lower abdominal surgery operations conducted in the UK each year, the cumulative costs of adhesion-related readmissions over 10 years are estimated at £569 Million. Conclusion Demonstrating the clinical effectiveness of adhesion reduction products in the RCT setting is unlikely to be feasible due to the large number of patients required. Products costing £200 or more are unlikely to payback their direct costs. 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