3 results
Search Results
Now showing 1 - 3 of 3
Item Intramolecular Hydrogen Bond in Biologically Active o-Carbonyl HydroquinonesAutores: Martinez-Cifuentes, M.; Weiss-Lopez, BE.; Santos, LS.; Araya-Maturana, R.Intramolecular hydrogen bonds (IHBs) play a central role in the molecular structure, chemical reactivity and interactions of biologically active molecules. Here, we study the IHBs of seven related o-carbonyl hydroquinones and one structurally-related aromatic lactone, some of which have shown anticancer and antioxidant activity. Experimental NMR data were correlated with theoretical calculations at the DFT and ab initio levels. Natural bond orbital (NBO) and molecular electrostatic potential (MEP) calculations were used to study the electronic characteristics of these IHB. As expected, our results show that NBO calculations are better than MEP to describe the strength of the IHBs. NBO energies (Delta E-ij((2))) show that the main contributions to energy stabilization correspond to LP ->sigma* interactions for IHBs, (O1O2)-O-center dot center dot center dot-H-2 and the delocalization LP ->pi* for O-2-C-2 = C-alpha(beta). For the (O1O2)-O-center dot center dot center dot-H-2 interaction, the values of Delta E-ij((2)) can be attributed to the difference in the overlap ability between orbitals i and j (F-ij), instead of the energy difference between them. The large energy for the LP O-2 ->pi* C-2 = C-alpha(beta) interaction in the compounds 9-Hydroxy-5-oxo-4,8, 8-trimethyl-1, 9(8H)-anthracenecarbolactone (VIII) and 9,10-dihydroxy-4,4-dimethylanthracen-1(4H)-one (VII) (55.49 and 60.70 kcal/mol, respectively) when compared with the remaining molecules (all less than 50 kcal/mol), suggests that the IHBs in VIII and VII are strongly resonance assisted.Item Biotransformation of Stypotriol triacetate by Aspergillus nigerAutores: Areche, C (Areche, Carlos)1;; Vaca, I (Vaca, Inmaculada)1;; Labbe, P (Labbe, Pamela)1;; Soto-Delgado, J (Soto-Delgado, Jorge)2;; Astudillo, L (Astudillo, Luis)3;; Silva, M (Silva, Mario)4;; Rovirosa, J (Rovirosa, Juana)1;; San-Martin, A (San-Martin, Aurelio)1Biological transformation of the meroditerpenoid, stypotriol triacetate (1) by the fungi Aspergillus niger, Cunninghamella elegans, Gibberella fujikuroi and Mucor plumbeus was studied. The incubation of 1 with A. niger yielded the new compound 6',14-diacetoxy-stypol-4,5-dione (2) whose structure was established by (1)H, (13)C and 2D NMR and supported by DFT/GIAO. (C) 2011 Elsevier B.V. All rights reserved.Item Identification of Antioxidant Methyl Derivatives of Ortho-Carbonyl Hydroquinones That Reduce Caco-2 Cell Energetic Metabolism and Alpha-Glucosidase ActivityAutores: Monroy Cárdenas, Matías Esteban; Almarza Chávez, Cristopher; Valenzuela Hormazábal, Paulina; Ramírez, David; Urra, Félix A.; Martínez Cifuentes, Maximiliano; Araya Maturana, Ramiro Juanalpha-glucosidase, a pharmacological target for type 2 diabetes mellitus (T2DM), is present in the intestinal brush border membrane and catalyzes the hydrolysis of sugar linkages during carbohydrate digestion. Since alpha-glucosidase inhibitors (AGIs) modulate intestinal metabolism, they may influence oxidative stress and glycolysis inhibition, potentially addressing intestinal dysfunction associated with T2DM. Herein, we report on a study of an ortho-carbonyl substituted hydroquinone series, whose members differ only in the number and position of methyl groups on a common scaffold, on radical-scavenging activities (ORAC assay) and correlate them with some parameters obtained by density functional theory (DFT) analysis. These compounds' effect on enzymatic activity, their molecular modeling on alpha-glucosidase, and their impact on the mitochondrial respiration and glycolysis of the intestinal Caco-2 cell line were evaluated. Three groups of compounds, according their effects on the Caco-2 cells metabolism, were characterized: group A (compounds 2, 3, 5, 8, 9, and 10) reduces the glycolysis, group B (compounds 1 and 6) reduces the basal mitochondrial oxygen consumption rate (OCR) and increases the extracellular acidification rate (ECAR), suggesting that it induces a metabolic remodeling toward glycolysis, and group C (compounds 4 and 7) increases the glycolysis lacking effect on OCR. Compounds 5 and 10 were more potent as alpha-glucosidase inhibitors (AGIs) than acarbose, a well-known AGI with clinical use. Moreover, compound 5 was an OCR/ECAR inhibitor, and compound 10 was a dual agent, increasing the proton leak-driven OCR and inhibiting the maximal electron transport flux. Additionally, menadione-induced ROS production was prevented by compound 5 in Caco-2 cells. These results reveal that slight structural variations in a hydroquinone scaffold led to diverse antioxidant capability, alpha-glucosidase inhibition, and the regulation of mitochondrial bioenergetics in Caco-2 cells, which may be useful in the design of new drugs for T2DM and metabolic syndrome.
