Phytochemical Screening and Antioxidant Activity of Seven Native Species Growing in the Forests of Southern Chilean Patagonia.

The genus is one of the most abundant in the subantarctic Patagonian forests. Five species inhabit these ecosystems, three evergreen (, , and ) and two deciduous ( and ). This is the first report on the levels of secondary metabolites and the antioxidant capacity of Patagonian tree species growing in natural environments.

FRI-1 Is an Anti-Cancer Isoquinolinequinone That Inhibits the Mitochondrial Bioenergetics and Blocks Metabolic Shifts by Redox Disruption in Breast Cancer Cells.

Since breast cancer (BC) cells are dependent on mitochondrial bioenergetics for promoting proliferation, survival, and metastasis, mitochondria highlight as an important target for anticancer drug discovery. FRI-1, methyl 1, 3-dimethyl-5, 8-dioxo-5, 8-dihydro-4-isoquinolinecarboxylate, was previously described as a selective cytotoxic compound on cancer cell lines, however, details on the mechanism of action remain unknown. In this work, we describe that FRI-1 inhibits mitochondrial bioenergetics, producing apoptosis in MCF7 and MDA-MB-231 BC cell lines.

Caffeates and Caffeamides: Synthetic Methodologies and Their Antioxidant Properties.

Polyphenols are secondary metabolites of plants and include a variety of chemical structures, from simple molecules such as phenolic acids to condensed tannins and highly polymerized compounds. Caffeic acid (3,4-dihydroxycinnamic acid) is one of the hydroxycinnamate metabolites more widely distributed in plant tissues. It is present in many food sources, including coffee drinks, blueberries, apples, and cider, and also in several medications of popular use, mainly those based on propolis.

FR58P1a; a new uncoupler of OXPHOS that inhibits migration in triple-negative breast cancer cells via Sirt1/AMPK/β1-integrin pathway.

Highly malignant triple-negative breast cancer (TNBC) cells rely mostly on glycolysis to maintain cellular homeostasis; however, mitochondria are still required for migration and metastasis. Taking advantage of the metabolic flexibility of TNBC MDA-MB-231 cells to generate subpopulations with glycolytic or oxidative phenotypes, we screened phenolic compounds containing an ortho-carbonyl group with mitochondrial activity and identified a bromoalkyl-ester of hydroquinone named FR58P1a, as a mitochondrial metabolism-affecting compound that uncouples OXPHOS through a protonophoric mechanism. In contrast to well-known protonophore uncoupler FCCP, FR58P1a does not depolarize the plasma membrane and its effect on the mitochondrial membrane potential and bioenergetics is moderate suggesting a mild uncoupling of OXPHOS.

Experimental and Theoretical Reduction Potentials of Some Biologically Active ortho-Carbonyl para-Quinones.

The rational design of quinones with specific redox properties is an issue of great interest because of their applications in pharmaceutical and material sciences. In this work, the electrochemical behavior of a series of four -quinones was studied experimentally and theoretically. The first and second one-electron reduction potentials of the quinones were determined using cyclic voltammetry and correlated with those calculated by density functional theory (DFT) using three different functionals, BHandHLYP, M06-2x and PBE0.

Small structural changes on a hydroquinone scaffold determine the complex I inhibition or uncoupling of tumoral oxidative phosphorylation.

Mitochondria participate in several distinctiveness of cancer cell, being a promising target for the design of anti-cancer compounds. Previously, we described that ortho-carbonyl hydroquinone scaffold 14 inhibits the complex I-dependent respiration with selective anti-proliferative effect on mouse mammary adenocarcinoma TA3/Ha cancer cells; however, the structural requirements of this hydroquinone scaffold to affect the oxidative phosphorylation (OXPHOS) of cancer cells have not been studied in detail. Here, we characterize the mitochondrial metabolism of TA3/Ha cancer cells, which exhibit a high oxidative metabolism, and evaluate the effect of small structural changes of the hydroquinone scaffold 14 on the respiration of this cell line.

Mitochondria: a promising target for anticancer alkaloids.

A great number of alkaloids exhibit high potential in cancer research. Some of them are anticancer drugs with well-defined clinical uses, exerting their action on microtubules dynamics or DNA replication and topology. On the other hand, mitochondria have been recognized as an essential organelle in the establishment of tumor characteristics, especially the resistance to cell death, high proliferative capacity and adaptation to unfavorable cellular environment.

NMR assignment in regioisomeric hydroquinones.

A set of regioisomeric pairs of tricyclic hydroquinones, analogues of antitumor 9,10-dihydroxy-4,4-dimethyl-5,8-dihydroanthracen-1(4H)-one (1) and other derivatives, were synthesized and their regiochemistry and NMR spectra assigned by using (1)H-detected one-bond (C-H) HMQC and long-range C-H HMBC, in good agreement with theoretical O3LYP/Alhrichs-pVTZ calculations. The 5-hydroxymethyl derivatives (11, 15, 19) showed a (3)J(H, H) coupling constant of methylene protons evidencing the presence of a seven-membered intramolecular hydrogen bonded ring, not observed for the 8-hydroxymethyl isomers.

Electrospray ionization mass spectrometric fragmentation of hydroquinone derivatives.

The fragmentation patterns of nine di-, tri- and tetracyclic hydroquinones with potential antitumor activity were rationalized by invoking competing mechanisms that included sterically accelerated homolytic cleavage, Meerwein-type rearrangements and dehydrations through elimination or intramolecular nucleophilic substitution.

8,8-Diethyl-1,4,5,8-tetra-hydro-naphthalene-1,4,5-trione.

The title mol-ecule, C(14)H(14)O(3), contains two fused six-membered carbon rings with keto groups at positions 1, 4 and 5 and a gem-diethyl group at position 8. The mol-ecule is close to planar (maximum deviation = 0.044 Å), with one ethyl group at each side of the mol-ecular plane, with exception of the keto group at position 1 which is slightly deviated from the plane and disordered over two positions one on each side of it (occupancies 0.

4-Acetyl-3,3-diethyl-5-hydr-oxy-2-morpholino-2,3-dihydro-1-benzofuran.

In the title compound, C(18)H(25)NO(4), the benzofuran ring is almost planar and the morpholino ring displays a chair conformation. The packing of compound has a one-dimensional structure constructed through inter-molecular O-H⋯O hydrogen bonds. The conformation is stabilized by intra-molecular C-H⋯N and C-H⋯O inter-actions.

9,10-Dihydr-oxy-4,4-dimethyl-5,8-dihydro-anthracen-1(4H)-one.

In the title mol-ecule, C(16)H(16)O(3), the ring system is planar and an intramolecular hydrogen bond is present. The mol-ecular packing is dominated by an inter-molecular hydrogen bond and by π-stacking inter-actions [inter-planar separation 3.8012 Å].