Decalactones, method for making, and pharmaceuticals there from

A novel class of decalactones with the general formula (I) and their stereoisomers is disclosed. A method for the synthesis of the decalactones of general formula (I) and the use of the decalactones in pharmaceutical compositions is also described

Targeting Mechanisms of the DNA Damage Response (DDR) and DNA Repair by Natural Compounds to Improve cAT-Triggered Tumor Cell Death

Recently, we identified secalonic acid F (SA), 5-epi-nakijiquinone Q (NQ) and 5-epi-ilimaquinone (IQ) as natural compounds (NC) affecting mechanisms of the DNA damage response (DDR). Here, we further characterized their effects on DDR, DNA repair and cytotoxicity if used in mono- and co-treatment with conventional anticancer therapeutics (cAT) (cisplatin (Cis), doxorubicin (Doxo)) in vitro. All three NC influence the phosphorylation level of selected DDR-related factors (i.e., pCHK1, pKAP1, pP53, pRPA32) in mono- and/or co-treatment. Both SA and NQ attenuate the Cis- and Doxo-induced G2/M-phase arrest and effectively stimulate caspase-mediated apoptosis. Notably, SA impacts DNA repair as reflected by enhanced steady-state levels of Cis-(1,2-GpG)-DNA adducts and Doxo-induced DNA double-strand breaks (DSB). Moreover, SA decreased the mRNA and protein expression of the homologous recombination (HR)-related DSB repair factors RAD51 and BRCA1. Both SA and NQ promote Cis- and Doxo-induced cytotoxicity in an additive to synergistic manner (CI ≤ 1.0). Summarizing, we conclude that SA promotes cAT-driven caspase-dependent cell death by interfering with DSB repair and DDR-related checkpoint control mechanisms. Hence, SA is considered as the most promising lead compound to evaluate its therapeutic window in forthcoming pre-clinical in vivo studies

TSG (2,3,5,4′-Tetrahydroxystilbene-2-O-β-D-glucoside) from the Chinese Herb Polygonum multiflorum Increases Life Span and Stress Resistance of Caenorhabditis elegans

2,3,5,4′-Tetrahydroxystilbene-2-O-β-D-glucoside (TSG) was isolated from Polygonum multiflorum, a plant which is traditionally used as an anti-ageing drug. We have analysed ageing-related effects of TSG in the model organism C. elegans in comparison to resveratrol. TSG exerted a high antioxidative capacity both in a cell-free assay and in the nematode. The antioxidative capacity was even higher compared to resveratrol. Presumably due to its antioxidative effects, treatment with TSG decreased the juglone-mediated induction of the antioxidative enzyme SOD-3; the induction of the GST-4 by juglone was diminished slightly. TSG increased the resistance of C. elegans against lethal thermal stress more prominently than resveratrol (50 μM TSG increased mean survival by 22.2%). The level of the ageing pigment lipofuscin was decreased after incubation with the compound. TSG prolongs the mean, median, and maximum adult life span of C. elegans by 23.5%, 29.4%, and 7.2%, respectively, comparable to the effects of resveratrol. TSG-mediated extension of life span was not abolished in a DAF-16 loss-of-function mutant strain showing that this ageing-related transcription factor is not involved in the effects of TSG. Our data show that TSG possesses a potent antioxidative capacity, enhances the stress resistance, and increases the life span of the nematode C. elegans

Anthraquinones and betaenone derivatives from the sponge-associated fungus Microsphaeropsis species : novel inhibitors of protein kinases

An undescribed fungus of the genus Microsphaeropsis, isolated from the Mediterranean sponge Aplysina aerophoba, produces two new betaenone derivatives (1, 2) and three new 1,3,6, 8-tetrahydroxyanthraquinone congeners (5-7). The structures of the compounds were established on the basis of NMR spectroscopic and mass spectrometric data and by CD spectroscopy. This is the first report wherein the (1)H and (13)C NMR data of the betaenone congeners are fully and unambiguously assigned on the basis of two-dimensional NMR spectroscopy. Furthermore, we describe the first elucidation of the absolute configuration of 1-(2'-anthraquinonyl)ethanols such as 5 and 6, by quantum chemical calculation of their circular dichroism (CD) and comparison with experimentally measured spectra. Moreover, it was shown that compounds 1, 5, 6, and 7 are inhibitors of PKC-epsilon, CDK4, and EGF receptor tyrosine kinases