Phenethyl Ester of Gallic Acid Ameliorates Experimental Autoimmune Encephalomyelitis

Gallic acid is a phenolic acid present in various plants, nuts, and fruits. It is well known for its anti-oxidative and anti-inflammatory properties. The phenethyl ester of gallic acid (PEGA) was synthesized with the aim of increasing the bioavailability of gallic acid, and thus its pharmacological potential. Here, the effects of PEGA on encephalitogenic cells were examined, and PEGA was found to modulate the inflammatory activities of T cells and macrophages/microglia. Specifically, PEGA reduced the release of interleukin (IL)-17 and interferon (IFN)-γ from T cells, as well as NO, and IL-6 from macrophages/microglia. Importantly, PEGA ameliorated experimental autoimmune encephalomyelitis, an animal model of chronic inflammatory disease of the central nervous system (CNS)—multiple sclerosis. Thus, PEGA is a potent anti-inflammatory compound with a perspective to be further explored in the context of CNS autoimmunity and other chronic inflammatory disorders.     

Food Peptides,Gut Microbiota Modulation,and Antihypertensive Effects

The gut microbiota is increasingly important in the overall human health and as such, it is a target in the search of novel strategies for the management of metabolic disorders including blood pressure, and cardiovascular diseases. The link between microbiota and hypertension is complex and this review is intended to provide an overview of the mechanism including the production of postbiotics, mitigation of inflammation, and the integration of food biological molecules within this complex system. The focus is on hydrolyzed food proteins and peptides which are less commonly investigated for prebiotic properties. The analysis of available data showed that food peptides are multifunctional and can prevent gut dysbiosis by positively affecting the production of postbiotics or gut metabolites (short-chain fatty acids, polysaccharides, biogenic amines, bile acids). Peptides and the postbiotics then displayed antihypertensive effects via the renin-angiotensin system, the gut barrier, the endothelium, and reduction in inflammation and oxidative stress. Despite the promising antihypertensive effect of the food peptides via the modulation of the gut, there is a lack of human studies as most of the works have been conducted in animal models.     

Selective oxidation of silanes into silanols with water using [MnBr(CO)5] as a precatalyst

The development of earth-abundant catalysts for the selective conversion of silanes to silanols with water as an oxidant generating valuable hydrogen as the only by-product continues to be a challenge. Here, we demonstrate that [MnBr(CO)₅] is a highly active precatalyst for this reaction, operating under neutral conditions and avoiding the undesired formation of siloxanes. As a result, a broad substrate scope, including primary and secondary silanes, could be converted to the desired products. The turnover performances of the catalyst were also examined, yielding a maximum TOF of 4088 h⁻¹. New light was shed on the debated mechanism of the interaction between [MnBr(CO)₅] and Si–H bonds based on the reaction kinetics (including KIEs of PhMe₂SiD and D₂O) and spectroscopic techniques (FT-IR, GC-TCD, ¹H-, ²⁹Si-, and ¹³C-NMR). The initial activation of [MnBr(CO)₅] was found to result from the formation of a manganese(i) hydride species and R₃SiBr, and the experimental data are most consistent with a catalytic cycle comprising a cationic tricarbonyl Mn(i) unit as the active framework.

This study presents the use of MnBr(CO)₅ for the selective conversion of silanes to silanols with water as an oxidant generating valuable hydrogen as the only by-product.     

Enantioselective crossed intramolecular [2+2] photocycloaddition reactions mediated by a chiral chelating Lewis acid

In intramolecular [2+2] photocycloaddition reactions, the two tethered olefins can approach each other in a straight or in a crossed fashion. Despite the fact that the latter reaction mode leads to intriguing, otherwise inaccessible bridged skeletons, there has so far not been any enantioselective variants thereof. This study concerned the crossed [2+2]-photocycloaddition of 2-(alkenyloxy)cyclohex-2-enones to bridged cyclobutanes. It was found that the reaction could be performed with high enantioselectivity (80–94% ee) under visible light conditions when employing a chiral rhodium Lewis acid as a catalyst (2 mol%).

An enantioselective crossed [2+2] photocycloaddition is presented which proceeds under visible light irradiation in the presence of a chiral Lewis acidic metal complex. Chelation of two oxygen atoms to the metal centre accounts for the observed enantioface differentiation.     

Discovery of an NAD+ analogue with enhanced specificity for PARP1

Among various protein posttranslational modifiers, poly-ADP-ribose polymerase 1 (PARP1) is a key player for regulating numerous cellular processes and events through enzymatic attachments of target proteins with ADP-ribose units donated by nicotinamide adenine dinucleotide (NAD⁺). Human PARP1 is involved in the pathogenesis and progression of many diseases. PARP1 inhibitors have received approvals for cancer treatment. Despite these successes, our understanding about PARP1 remains limited, partially due to the presence of various ADP-ribosylation reactions catalyzed by other PARPs and their overlapped cellular functions. Here we report a synthetic NAD⁺ featuring an adenosyl 3′-azido substitution. Acting as an ADP-ribose donor with high activity and specificity for human PARP1, this compound enables labelling and profiling of possible protein substrates of endogenous PARP1. It provides a unique and valuable tool for studying PARP1 in biology and pathology and may shed light on the development of PARP isoform-specific modulators.

An analogue of nicotinamide adenine dinucleotide (NAD⁺) featuring an azido group at 3′-OH of adenosine moiety is found to possess high specificity for human PARP1-catalyzed protein poly-ADP-ribosylation.     

Über eine Mikrobestimmung des Acetons und derβ-Oxybuttersäure berichtet

Analytical and Bioanalytical Chemistry -