Application of 609-14-3In 2021 ,《Umbelliferyloxymethyl phosphonate compounds-weakly binding zinc ionophores with neuroprotective properties》 appeared in Dalton Transactions. The author of the article were Guesne, Sebastien; Connole, Laura; Kim, Stephanie; Motevalli, Majid; Robson, Lesley; Michael-Titus, Adina T.; Sullivan, Alice. The article conveys some information:
Umbelliferone is a member of the coumarin family of compounds which are known for diverse pharmacol. activity including in targets relevant to Alzheimers disease, AD. The toxicity associated with some forms of the amyloid protein, Aβ, and the role of Zn2+ (and other biometals) dyshomeostasis in this, are of great interest in AD and make metal ionophore capability desirable in so called multi target drug ligands MTDLs. A new series of umbelliferyloxymethyl phosphonic acid diethylester compounds (umbelliferyloxymethyl phosphonates) bearing a phosphonate at the 7-position (compounds 1, 3-6), hydrolysis products 2, 2a and 2b from 1 and analogs 7 and 8 of 1 with 7-O to 7-S and 1-O to 1-NH substitutions, are reported. Single crystal x-ray structures of compounds 1, 2 and 2a were determined In terms of neuroprotective properties, the compounds 1, 2, 3, 4, 5 and 6 at 1μM concentration, inhibited the toxicity of Aβ1-42 (Aβ42) in both toxic Amyloid Derived Diffusible Ligand (ADDL) and fibrillar (fibril) forms towards rat hippocampal cells. Compound 7 displayed cytotoxicity and 8 failed to inhibit Aβ42 toxicity. Concerning compound-metal ionophore activity (assessed using chem. experiments), despite weak binding to Zn2+ determined from 31P NMR titration of 1 and 2 by ZnCl2, compounds 1, 3, 4, 5 and 6 demonstrated ionophore assisted partition of Zn2+ from water to octanol at micromolar concentrations with efficacy on a par with or better than the chelator MTDL clioquinol (5-chloro-7-iodo-8-hydroxyquinoline). Partition was assessed using furnace Atomic Absorption Spectroscopy (AAS). In further experiments interaction of compound 1 with Zn2+ or it’s pathways was inferred by (i) delayed fluorescence response with added Zn2+ in cells treated with FluoZin-3 and (ii) by suppression of Zn2+ promoted aggregation of Aβ42. The results came from multiple reactions, including the reaction of Ethyl 2-methyl-3-oxobutanoate(cas: 609-14-3Application of 609-14-3)
Ethyl 2-methyl-3-oxobutanoate(cas: 609-14-3) belongs to ketone compounds. They are most widely used as solvents, especially in industries manufacturing explosives, lacquers, paints, and textiles. Ketones are also used in tanning, as preservatives, and in hydraulic fluids.Application of 609-14-3
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