1.Synthesis, crystal structure and biological activities of a novel amidrazone derivative and its copper(II) complex--a potential antitumor drug.
Mazur L1, Modzelewska-Banachiewicz B, Paprocka R, Zimecki M, Wawrzyniak UE, Kutkowska J, Ziółkowska G. J Inorg Biochem. 2012 Sep;114:55-64. doi: 10.1016/j.jinorgbio.2012.04.021. Epub 2012 May 10.
A new linear amidrazone derivative, 6-acetyl-cyclohex-3-enecarboxylic acid [1-pyridin-2-yl-1-(pyridyn-2-yloamin)meth-(Z)-ylidene] hydrazide, H(2)L (2) and its Cu(II) complex, [Cu(2)L(2)]·4H(2)O (3) were synthesized and characterized by elemental analysis, IR and (1)H NMR spectroscopy and cyclic voltammetry. Compound 2 was synthesized in the equimolar reaction of N(3)-substituted amidrazone with cis-1,2,3,6-tetrahydrophthalic anhydride. The Cu complex of 2 was obtained in the reaction with copper(II) acetate. The molecular structures of 2 and 3 were determined by X-ray crystallography. The parent ligand exists in its amide-hydrazone form in the solid state. The central amidrazone moiety has a Z configuration with respect to the double C=N bond. Coordination to the metal center promotes Z/E isomerization of the hydrazone group of the ligand. Compound 3 is a dinuclear four-coordinated Cu(II) complex with the amidrazone ligand behaving as a tetradentate double deprotonated chelating one.
2.Mono- and bis-quinidine organocatalysts in the asymmetric methanolysis of cis-1,2,3,6-tetrahydrophthalic anhydride: a conformational and mechanistic NMR study.
Balzano F1, Jumde RP, Mandoli A, Masi S, Pini D, Uccello-Barretta G. Chirality. 2011 Oct;23(9):784-95.
The enantioselective organocatalytic methanolysis of cis-1,2,3,6-tetrahydrophthalic anhydride mediated by quinidine derivatives with pyridazine or anthraquinone core was investigated, carrying out a detailed nuclear magnetic resonance study of the conformational preferences of the alkaloid catalysts in the pure solvent and in the presence of the reaction substrates and products. No significant interaction between the meso-anhydride and the alkaloid derivatives was detected. In contrast, evidence for a considerable influence of the alcohol reactant on the conformational state of some of the chiral organocatalysts could be obtained, which lends support to the hypothesis of general-base catalysis mechanism, as opposed to the nuclephilic one. The catalytic properties of the studied derivatives showed no obvious correlation with their conformational prevalence in the resting state, suggesting that the alkaloid 9-O substituent should have a more active role than merely enforcing the chiral fragments to adopt a preferential reactive conformation.
3.Structure-activity relationships of organic acid anhydrides as antigens in an animal model.
Welinder H1, Zhang X, Gustavsson C, Björk B, Skerfving S. Toxicology. 1995 Nov 30;103(2):127-36.
Relationships between chemical structure and immunogenicity have been studied in 13 dicarboxylic acid anhydrides. Guinea-pigs were immunized intradermally by a single dose of 0.3 M solutions of succinic anhydride (SA), maleic anhydride (MA), methylmaleic anhydride (MMA), cis-cyclohexane-1,2-dicarboxylic anhydride (cis-HHPA), trans-cyclohexane-1,2-dicarboxylic anhydride (trans-HHPA), 4-methylcyclohexane-1,2-dicarboxylic anhydride (MHHPA), cis-1,2,3,6-tetrahydrophthalic anhydride (THPA1236), cis-3,4,5,6-tetrahydrophthalic anhydride (THPA3456), cis-3-methylcyclohex-4-ene-1,2-dicarboxylic anhydride (MTHPA34), cis-4-methylcyclohex-4-ene-1,2-dicarboxylic anhydride (MTHPA44), phthalic anhydride (PA), 4-methylphthalic anhydride (MPA), and trimellitic anhydride (TMA) in olive oil. Specific IgE, IgG, IgG1, and IgG2 antibodies against guinea-pig serum albumin conjugates of the anhydrides were determined by passive cutaneous anaphylaxis (PCA) tests and enzyme-linked immunoabsorbant assay (ELISA).
4.Antinociceptive effects of tetrahydrophthalimides and related compounds.
Costa BB1, Corrêa R, De Souza MM, Pretto JB, Ardenghi JV, De Campos-Buzzi F, Cechinel Filho V. Z Naturforsch C. 2007 Mar-Apr;62(3-4):201-6.
This paper describes the antinociceptive effects of tetrahydrophthalimides and related compounds in mice. Twenty compounds were obtained by the reaction of cis-1,2,3,6-tetrahydrophthalic anhydride with appropriate amines, dehydration, and addition to the imidic double bond. They were analyzed in the writhing test at 10 mg/kg given intraperitoneally. The most active compound 2-benzyl-5-morpholin-4-yl-hexahydroisoindole-1,3-dione (19) was studied on formalin, capsaicin, glutamate and hot plate models. The antinociceptive activity demonstrated by some studied compounds is promising, and some of them were more active than acetylsalicylic acid and paracetamol used as reference drugs in writhing tests in mice. Compound 19 was about 5-fold more potent than the reference drugs, being also effective by oral route and against the inflammatory response in the formalin test. The results suggest that compound 19 could be used as a model to obtain new and more potent antinociceptive agents.