The thermodynamic landscape of carbon redox biochemistry

Redox biochemistry plays a key role in the transduction of chemical energy in all living systems. Observed redox reactions in metabolic networks represent only a minuscule fraction of the space of all possible redox reactions. Here we ask what distinguishes observed, natural redox biochemistry from the space of all possible redox reactions between natural and non-natural compounds. We generate the set of all possible biochemical redox reactions involving linear chain molecules with a fixed numbers of carbon atoms. Using cheminformatics and quantum chemistry tools we analyze the physicochemical and thermodynamic properties of natural and non-natural compounds and reactions. We find that among all compounds, aldose sugars are the ones with the highest possible number of connections (reductions and oxidations) to other molecules. Natural metabolites are significantly enriched in carboxylic acid functional groups and depleted in carbonyls, and have significantly higher solubilities than non-natural compounds. Upon constructing a thermodynamic landscape for the full set of reactions as a function of pH and of steady-state redox cofactor potential, we find that, over this whole range of conditions, natural metabolites have significantly lower energies than the non-natural compounds. For the set of 4-carbon compounds, we generate a Pourbaix phase diagram to determine which metabolites are local energetic minima in the landscape as a function of pH and redox potential. Our results suggest that, across a set of conditions, succinate and butyrate are local minima and would thus tend to accumulate at equilibrium. Our work suggests that metabolic compounds could have been selected for thermodynamic stability, and yields insight into thermodynamic and design principles governing nature’s metabolic redox reactions.https://www.biorxiv.org/content/10.1101/245811v1Othe

Slim and scum: Natural products from land and sea

To a natural-products chemist, the term "natural products" does not refer to all compounds from natural sources, as the name might imply. It is specifically used to refer to compounds known as secondary metabolites, structurally complex molecules, often of unknown function, with very limited biological distribution

Prevention of Protein Glycation by Natural Compounds

Non-enzymatic protein glycosylation (glycation) contributes to many diseases and aging of organisms. It can be expected that inhibition of glycation may prolong the lifespan. The search for inhibitors of glycation, mainly using in vitro models, has identified natural compounds able to prevent glycation, especially polyphenols and other natural antioxidants. Extrapolation of results of in vitro studies on the in vivo situation is not straightforward due to differences in the conditions and mechanism of glycation, and bioavailability problems. Nevertheless, available data allow to postulate that enrichment of diet in natural anti-glycating agents may attenuate glycation and, in consequence, ageing

Nirs tools for prediction of main extractives compounds of teak (Tectona grandis L.) heartwood

Biochemical and physiological process which occurred during heartwood formation have consequences on wood properties such as colour, natural durability and some mechanical properties. However, it is very time-consuming to take measurements of extractives contents. Teak has been reported to contain 1-hydroxy- 2-methyl-anthraquinone, 2-hydroxy-methyl-anthraquinone, 2-methyl- anthraquinone, lapachol, 1,4-naphthoquinone for the main compounds. In teak, natural durability is ascribed to extractives. Consequently, it's possible to estimate natural durability by measurement of extractives indirectly. For the purposes of selection for the production of improved varieties, the number of samples to be measured rapidly exceeds the capacity of a traditional laboratory. Near-infrared spectroscopy approach, based on spectral data and reference data, is a tool enabling many of the chemical properties of wood to be predicted and the number of laboratory measurements to be reduced exponentially. The issue here is a question of checking the effectiveness of NIRS tool to build models and predict the main extractive compounds of teak wood from Ivory Coast. We try to calibrate these chemical properties with Nirs spectral information measured on grounded wood. The results show the possible use of NIRS to predict total phenol content and some main extractive compounds of teak heartwood as tectoquinone, 2-hydroxymethylanthraquinone,Consequently, after verification on other sets of teak samples, which may or may not be included in the prediction model, NIRS can be used to predict extractive compounds accurately for a large number of samples, making it possible to estimate natural durability indirectly and to include these characteristics in the selection criteria for classifying wood and high throughput phenotyping. (Résumé d'auteur

Natural Compounds: Molecular Weapons against Leukemia\u2019s

Nowadays cancer is one of the main reasons of death all over the world and it is estimated that deaths caused by cancer will grow dramatically in the next decades. Even if chemotherapy is the election therapy for solid tumors, as well as leukemias and lymphomas, cancer treatments are in continuous evolution trying to solve the problem of resistance mainly due to low accumulation of the drug in tumor cells (MDR). Natural compounds represent a valid alternative to treat several disease and recently the scientific community focus on these natural compounds and plant metabolites with therapeutic activities and low toxicities compared with synthetic ones. A combination therapy, that join conventional chemotherapy with natural plant metabolites, is now considered a new promising strategy to overcome MDR and reduce cellular toxicity; in particular, in leukemia due to its very complex origin and development of leukemogenesis. Here, we want to summarize and update the recent applications of natural compounds in the treatment of leukemia

Natural Compounds as Beneficial Antioxidant Agents in Neurodegenerative Disorders: A Focus on Alzheimer’s Disease

The positive role of nutrition in chronic neurodegenerative diseases (NDs) suggests that dietary interventions represent helpful tools for preventing NDs. In particular, diets enriched with natural compounds have become an increasingly attractive, non-invasive, and inexpensive option to support a healthy brain and to potentially treat NDs. Bioactive compounds found in vegetables or microalgae possess special properties able to counteract oxidative stress, which is involved as a triggering factor in neurodegeneration. Here, we briefly review the relevant experimental data on curcuminoids, silymarin, chlorogenic acid, and compounds derived from the microalga Aphanizomenon flos aquae (AFA) which have been demonstrated to possess encouraging beneficial eects on neurodegeneration, in particular on Alzheimer’s disease models

Synthesis of New Analogues of the Bengamides: Peptidyl Bengamides and Molecular Probes

Isolated from sponges of the Jaspidae family, first members where discovered in 1986. The bengamides represent an interesting and unprecedented family of natural products that displayed striking antitumor activities [1]. The recognition of these natural products as antiangiogenic compounds, in virtue to their inhibition of methionine aminopeptidases, prompted intense research activities in the chemical and biological fields. In fact, the total synthesis of the natural products, together with an extensive variety of analogues, has been reported in the literature [2]. Particularly, we have recently developed a new synthetic methodology which allowed rapid and efficient access to the natural bengamide E (1), together with a wide library of analogues of which the cyclopentyl analogue 2 was identified as a more potent antitumor compound with respect to its natural congener [3]. As continuation of these synthetic efforts, with the objective of identifying new potent and promising analogues, we wish to report our recent synthetic studies directed to the synthesis of new bengamide analogues, featured by the replacement of the caprolactam fragment by a peptidyl residue (compounds type 3). On the other hand, in order to gain insight into the mechanism of the biological action of the bengamides, we describe the preparation of the N-alkyl derivatives 4 and 5, which represent interesting molecules that could be employed as suitable molecular probes.Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech

REPCO contribution to the development of products for apple scab control

Natural compounds were sprayed according the RimPro scab warning system from start of bud break until the mid of June. Scab incidence was measured on the leaves and the fruit. Phytotoxicitiy and russet-ing was assessed. The natural compounds were sprayed together with sulphur and were compared with the standard biological fungicides copper hy-droxide and sulphur alone. Compound E73 + sulphur was the most effective on fruit. Armicarb and Resis-tim both sprayed with sulphur were comparable in efficacy with Funguran-OH. In our study laminarin (GL 32) did not shown any effect on the control of scab on apple

Antioxidant and Anti-Inflammatory Activities of Flavanones from Glycyrrhiza glabra L. (licorice) Leaf Phytocomplexes: Identification of Licoflavanone as a Modulator of NF-kB/MAPK Pathway

Inflammation represents an adaptive response generated by injuries or harmful stimuli. Natural remedies represent an interesting alternative to traditional therapies, involving several biochemical pathways. Besides, the valorization of agrochemical wastes nowadays seems to be a feasible way to reduce the health spending and improve the accessibility at bioactive natural compounds. In this context, the chemical composition of three Glycyrrhiza glabra L. (licorice) leaf extracts, obtained through maceration or ultrasound-assisted method (fresh and dried leaves) was investigated. A guided fractionation obtained three main components: pinocembrin, glabranin and licoflavanone. All the extracts showed similar antioxidant properties, evaluated by 2,2'-diphenyl-1-picrylhydrazyl (DPPH) or 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) Diammonium Salt (ABTS) assay, while, among the isolated compounds, licoflavanone exhibited the best antioxidant activity. The anti-inflammatory activity of the extracts and the purified compounds was investigated in lipopolysaccharide (LPS)-stimulated RAW 264.7 murine macrophages. Extract C and licoflavanone showed a good anti-inflammatory activity without affecting cell viability, as they decreased nitrite levels even when used at 12.5 μg/mL (p < 0.005) and 50 μM concentration (p < 0.001), respectively. Interestingly, licoflavanone markedly decreased pro-inflammatory cytokines and cyclooxygenase 2/inducible nitric oxide synthase (COX-2/iNOS) expression levels (p < 0.001). A modulation of nuclear factor kappa B/mitogen-activated protein kinases (NF-kB/MAPK) pathway underlay such behavior, highlighting the potential of this natural compound as a new scaffold in anti-inflammatory drug research

Microbial demethylation of dimethylsulfoniopropionate and methylthiopropionate

As discussed in chapter 1 , there is an increased interest in the production of certain natural sulfur-containing flavor compounds or flavor precursors. Production of natural flavors is becoming increasingly important, because consumerts end to prefer natural compounds for health reasons. With the aid of extraction techniques it is possible to obtain flavors directly from plant material, but these methods are time consuming and expensive, because the most interesting flavors are present in only very low concentrations. A more recent method to produce flavors is based on a biotechnological approach where natural precursors, isolated mainly from plant material, can be convertedt o the desired flavor in a bioreactor with the aid of enzymes and/or microorganisms.