1152-62-1Relevant articles and documents
A Model for the Active Sites of Oxo-Transfer Molybdoenzymes: Reactivity, Kinetics, and Catalysis
Berg, Jeremy M.,Holm, R. H.
, p. 925 - 932 (1985)
Oxidation-reduction reactions of substrates in systems containing the complexes Mo(VI)O2(LNS2) and Mo(IV)O(LNS2)(DMF) (LNS2=2,6-bis(2,2-diphenyl-2-mercaptoethyl)pyridine) in DMF solutions at 23 deg C have been investigated as models for the activities of certain oxo-transfer molybdoenzymes.The MoO1,2S2N coordination units are resonable representations of this class of enzymes.MoO2(LNS2) reacts with Ph3P in a second-order process to yield MoO(LNS2)(DMF) and Ph3O with the rate constant k1=7(1)*10-3 M-1 s-1.MoO(LNS2)(DMF) reduces sulfoxides in a two-stage reaction involving equilibrium formation of the R2SO adduct (K=4.2-16*103) followed by R2S formation (k1=1.36-1.70*10-3 s-1).The small dependence of K and k1 on substrate structure suggests that the adduct is O-ligated to Mo(IV).These reactions exhibit the frequent enzymatic property of substrate saturation kinetics.One substrate is d-biotin d-(S-oxide), the natural substrate of the Mo-dependent enzyme biotin S-oxide reductase from E. coli, indicating the biological significance of the reactions.Evidence concerning this and other physiological sulfoxide reducing activities is summarized.Oxo transfers to and from substrate have been coupled to produce a catalytic system which turns over the reaction Me2SO+Ph3P->Me2S+Ph3PO, in which Me2SO serves as a model substrate.No reaction is observed in the absence of the Mo catalyst.The initial catalytic rate is given by k, with k=6*10-3 M-1 s-1.This rate is limited by the rate of reduction of MoO2(LNS)2 by Ph3P.The sulfoxide reducing system developed here is characterized by substrate saturation kinetics, transformation of a biological substrate, and a well-defined catalytic cycle capable of turnover of hundreds of equivalents of a model substrate without intervention of a physiologically unrealistic μ-oxo-Mo(V) dimer.This system joins others recently devised in a broad development of reactivity models of metalloenzymes.
Symmetric benzidine derivatives as anti-HCV agents: Insight into the nature, stereochemistry of the capping amino acid and the size of the terminal capping carbamates
Abadi, Ashraf H.,Abdel Karim, Shereen E.,Abdel-Halim, Mohammad,Ahmed, Nermin S.,Frakolaki, Efseveia,Vassilaki, Niki,Youssef, Youssef H.,Zoidis, Grigoris
, (2020/07/27)
Novel symmetric molecules, bearing a benzidine prolinamide core, two terminal carbamate caps of variable sizes and nature, including natural and unnatural amino acids were developed. Several terminal N-carbamate substituents of the core structure, ranging from linear methyl, ethyl and butyl groups to branching isobutyl group; and an aromatic substituent were also synthesized. Series 1 has hydrophobic AA residues, namely S and R phenylglycine and a terminal carbamate capping group, whereas Series 2 bears sulphur containing amino acids, specifically S and R methionine and the natural R methylcysteine. The novel compounds were tested for their inhibitory activity (EC50) and their cytotoxicity (CC50), using an HCV 1b (Con1) reporter replicon cell line. Compound 4 with the unnatural capping residue, bearing D-Phenylglycine amino acid residue and N-isobutyloxycarbonyl capping group, was the most active within the two series, with EC50 = 0.0067 nM. Moreover, it showed high SI50 > 14788524 and was not cytotoxic at the highest tested concentration (100 μΜ), indicating its safety profile. Compound 4 also inhibited HCV genotypes 2a, 3a and 4a. Compared to the clinically approved NS5A inhibitor Daclatasvir, compound 4 shows higher activity against genotypes 1b and 3a, as well as improved safety profile.
A kind of amino acid tanshinone phenolic derivative and its preparation method
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Paragraph 0085, (2016/10/09)
The invention relates to amino acid tanshinone phenolic ester derivatives and a preparation method thereof. The derivatives are obtained by reducing tanshinone compounds and performing esterified modification on the reduced tanshinone compounds and an amino acid into prodrugs, wherein the tanshinone compounds are phenanthrenequinone compounds which exist in salvia miltiorrhiza and have an o-quinone structure; the esterified amino acid is alpha-amino acid. The amino acid tanshinone phenolic ester derivatives are compounds having a structure of a general formula (I) or medicinal salts thereof, wherein R1 and R2 represent H or acyl alpha-amino acid and a salt thereof, and R1 and R2 are not H at the same time. The amino acid tanshinone phenolic ester derivatives have the beneficial effects that firstly, the new tanshinone derivatives are provided and the new substances have potential treatment effect on some serious diseases such as tumors, and secondly, amino acid tanshinone phenolic ester derivatives have excellent water solubility and thus can be prepared into injections conveniently in addition to various oral preparations, and therefore, the amino acid tanshinone phenolic ester derivatives are capable of quickly taking effect in disease treatment. As important prodrugs, the amino acid tanshinone phenolic ester derivatives have important application value.