RESUMO
Long-range coupling constants (5) JHortho,OMe were measured in series of methoxyindoles, methoxycoumarins, and methoxyflavones by the modified J doubling in the frequency domain method. The COSY and NOESY spectra revealed the coupling of the -OMe group with a specific proton at the ortho position and its preferred conformation. Homonuclear (1) H-(1) H couplings were confirmed by irradiation of the -OMe signal. Density functional theory calculations of (5) JHortho,OMe using the modified aug-cc-pVTZ basis set evidenced that the Fermi contact term shows good agreement with the experimental J values. Accurate chemical shift and coupling constant values followed after iterative quantum mechanical spectral analysis using the PERCH software.
RESUMO
1,2,3,4,6-Penta-O-acetyl-α-D-glucopyranose and the corresponding [1-(2)H], [2-(2)H], [3-(2)H], [4-(2)H], [5-(2)H], and [6,6-(2)H(2)]-labeled compounds were prepared for measuring deuterium/hydrogen-induced effects on (13)C chemical shift (n)Δ (DHIECS) values. A conformational analysis of the nondeuterated compound was achieved using density functional theory (DFT) molecular models that allowed calculation of several structural properties as well as Boltzmann-averaged (13)C NMR chemical shifts by using the gauge-including atomic orbital method. It was found that the DFT-calculated C-H bond lengths correlate with (1)Δ DHIECS.
Assuntos
Deutério/química , Glucose/análogos & derivados , Isótopos de Carbono , Glucose/química , Hidrogênio/química , Espectroscopia de Ressonância Magnética/normas , Teoria Quântica , Padrões de ReferênciaRESUMO
Among various phenolic compounds, caffeic acid (3,4-dihydroxycinnamic acid) exhibited pharmacological antioxidant, anticancer and antimutagenic activities. The antioxidant properties of phenolic compounds depend on their chemical structure, however, the role of the ethylenic side chain in the radical scavenging activity remains controversial. Thus, the aim of this study consisted to test cinnamic acid and 15 cinnamic acid derivatives in the well known CCl(4)-induced acute liver damage model, which is dependent on oxidative stress mechanisms. Cinnamic acid and 15 cinnamic acid derivatives (50 mg/kg, p.o.) were administered to male Wistar rats intoxicated with CCl(4) (4 g/kg, p.o.). The activities of gamma-glutamyl transpeptidase, alkaline phosphatase and alanine aminotransferase were measured in serum. The lipid peroxidation products were determined in liver. Compounds with a methoxy group at position 3 or 4, or a 3,4-methylenedioxy moiety were the most active ones. Also, we observed that the monosubstituted 3 or 4 hydroxy, or the bulky 3,4 dibenzyloxy substituted compounds showed lower activity. The poorest activity was displayed by disubstituted 3,4-dihydroxy, dimethoxy or diacetyl cinnamic acid derivatives, the ester derived from cinnamic acid with an 8 carbon chain and N-dimethyl substituted compound. Thus, the methoxy substituted group at positions 3 or 4 or the 3,4-methylenedioxy moiety in the caffeic acid derivatives; seem to be the main features required for the hepatoprotection in this model.
Assuntos
Cinamatos/farmacologia , Fígado/efeitos dos fármacos , Animais , Tetracloreto de Carbono/toxicidade , Masculino , Ratos , Ratos Wistar , Relação Estrutura-AtividadeRESUMO
1H and 13C NMR chemical shift assignments for the urinary tract antispasmodic flavoxate (1) and flavoxate hydrochloride (2) were obtained from one- and two-dimensional measurements. A Monte Carlo random search using molecular mechanics, followed by geometry optimization of each minimum energy structure employing DFT calculations at the B3LYP/6-31G* level, and a Boltzmann analysis of the total energies, provided accurate molecular models which describe the conformational behavior of flavoxate (1). The electron density surfaces for the global minimum and the second minimum conformers 1a and 1b of this L-type Ca2+ channel inhibitor were calculated. The presence of both conformers in solution was demonstrated in full agreement with 2D NOESY data and NOE difference spectroscopy.
Assuntos
Flavoxato/química , Espectroscopia de Ressonância Magnética , Parassimpatolíticos/química , Simulação por Computador , Modelos Moleculares , Conformação Molecular , Método de Monte Carlo , Sistema UrinárioRESUMO
The reactions of 5-substituted indolylmalonates (2a-e), carrying an electron-withdrawing group at the N(1) position, with bromine in CCl(4) or AcOH are reported. These substrates undergo oxidation in competition with the well-known aromatic bromination. Under the two sets of conditions, with parent indolylmalonate (2a), chemospecific oxidation is observed, whereas with 5-hydroxyindolylmalonate (2c), bromination at the 4- and 6-position is the dominating reaction. Investigation of the products composition of several 5-substituted indolylmalonates revealed the following trend: with a 5-substituted electron-withdrawing group like fluorine, the indolylmalonate undergoes oxidation rather than bromination. In contrast, with a 5-substituted electron-donating group, like a hydroxyl group, the ring bromination occurs preferentially over the oxidation. When the 5-substituent is an alkoxyl group, a significant amount of brominated-oxidized products is obtained. Monitoring the oxidation reaction by mass spectrometry allowed the characterization of the 2-bromoindolylidenemalonate intermediate. A bromonium ion is considered as possible pathway in the formation of this intermediate. The conformation of unsymmetrical methoxyl and benzyloxyl substituents was determined from (1)H NMR spectra, single-crystal X-ray diffraction and ab initio calculations.