Efficient synthesis and biological evaluation of two modafinil analogues

Non classical bioisosters of modafinil featuring interesting biological profile have been easily produced through replacement of the sulfoxide function with a carbonyl group and modification of the carboxylic acid amide functionality.     

Response of membrane-bound ATPase ofMicrococcus luteus to heat and ultraviolet light

Summary It is shown that the properties of ATPase (EC 3.6.1.3) ofMicrococcus luteus depend only to some extent on the state of the membrane to which it is attached. Its interaction with the membrane appears to be largely controlled by polar forces. It is shown, however, that the UV-sensitivity of the membrane-bound ATPase is also significantly influenced by the state of membrane lipids.

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Zusammenfassung Es wird gezeigt, daß das Verhalten der membrangebundenen ATPase (EC 3.6.1.3) inMicrococcus luteus im allgemeinen wenig vom Zustand der Membran abhängt. Ihre Wechselwirkung mit der Membran wird offenbar weitgehend durch polare Kräfte bestimmt. Jedooh zeigt die UV-Inaktivierung der membrangebundenen ATPase, daß ihre UV-Empfindlichkeit und damit ihr Zustand nicht völlig unabhängig von der Struktur der Membran-Lipide beurteilt werden darf.

     

Mechanisms by which autophagy regulates memory capacity in ageing

Autophagy agonists have been proposed to slow down neurodegeneration. Spermidine, a polyamine that acts as an autophagy agonist, is currently under clinical trial for the treatment of age‐related memory decline. How Spermidine and other autophagy agonists regulate memory and synaptic plasticity is under investigation. We set up a novel mouse model of mild cognitive impairment (MCI), in which middle‐aged (12‐month‐old) mice exhibit impaired memory capacity, lysosomes engulfed with amyloid fibrils (β‐amyloid and α‐synuclein) and impaired task‐induced GluA1 hippocampal post‐translation modifications. Subchronic treatment with Spermidine as well as the autophagy agonist TAT‐Beclin 1 rescued memory capacity and GluA1 post‐translational modifications by favouring the autophagy/lysosomal‐mediated degradation of amyloid fibrils. These findings provide new mechanistic evidence on the therapeutic relevance of autophagy enhancers which, by improving the degradation of misfolded proteins, slow down age‐related memory decline.     

Proteasome inhibitors; synthesis and activity of arecoline oxide tripeptide derivatives

We describe the synthesis and biological activities of a series of methyl 3,4-epoxypiperidine-3-carboxylate tripeptide derivatives that inhibit the chymotryptic and tryptic active sites of the 20S proteasome. Of the series, compound 2 which contains 3-hydroxy-2-methylbenzoyl group at its N-terminal position, displayed the greatest inhibitory potency (IC(50) <1 microM). All derivatives showed favourable pharmacokinetic properties.     

Influence of serotonin on some serum enzyme activities in rats

The serotonin injected intraperitoneally in rats (20 mg/Kg of body weight) modifies some seric enzymatic activities (LDH, alpha-HBDH and CPK) at different times from the injection (30, 60, 90 min.), acting probably on membrane permeability and on intracellular metabolism.     

Chemical characterisation,antioxidant and antimicrobial screening for the revaluation of wine supply chain by-products oriented to circular economy

Abstract

Aim of the project was the bioassay guided optimisation of extraction methods applied to wine chain by-product to obtain extracts, fractions and biologically active biomolecules with a possible use in the nutraceutical and cosmeceutical industry. Exhausted red and white grape marc were extracted using water:ethanol 50:50 with ultrasound assisted extraction and Naviglio® technology; and also with supercritical fluid extraction (SFE) and steam-distillation obtaining different phytocomplexes. Each extract was characterised by different molecular category: exhausted red grape marc (VCR) by anthocyanins, exhausted white grape marc (VCB) by flavonoids, and grapeseed (VIN) by proanthocyanins. SFE and steam-distillation, instead, highlighted the presence of fatty acids and their ester in every matrix, but terpenoids were not revealed at level major or equal than 0.1%, except for manoyl oxide in VCR (2.89%). VIN was the most abundant matrix in polyphenols (506.24?±?55.91?mg gallic acid/g dried extract), and it showed the highest antioxidant activity (IC₅₀ of 4.30?μg/mL). Regarding the antimicrobial activity, the hydroalcoholic extracts from VCR, VCB and VIN were tested but no noteworthy activities have been recorded.     

Survival of Microorganisms under the Extreme Conditions of the Atacama Desert

Spores of Bacillus subtilis, conidia of Aspergillus niger, versicolor and ochraceus andcells of Deinococcus radiodurans have been exposed in the dark at two locations (at about 23°S and 24°S) in the Atacama Desert for up to 15 months. B. subtilis spores (survival 15%) and A. niger conidia (survival 30%) outlived the other species. The survival of the conidiaand spores species was only slightly poorer than that of thecorresponding laboratory controls. However, the Deinococcus radiodurans cells did not survive the desertexposure, because they are readily inactivated at relativehumidities between 40 and 80% which typically occurduring desert nights. Cellular monolayers of the dry sporesand conidia have in addition been exposed to the full sunlight for up to several hours. The solar fluences causing 63% loss in viability (F₃₇-values) have been determined.These F₃₇-values are compared with those determined atother global locations such as Punta Arenas (53°S), Key Largo (25°N) or Mainz (50°N) during the same season. Thesolar UVB radiation kills even the most resistantmicroorganisms within a few hours due to DNA damages. Thedata are also discussed with respect to possible similaritiesbetween the climatic conditions of the recent Atacama Desertand the deserts of early Mars.     

F1-ATPase from Micrococcus sp. ATCC 398. Purification by ion-exchange chromatography and further characterization. (Auto)proteolysis and dissociative effects.

The preparation of highly purified F1-ATPase from Micrococcus sp. ATCC 398 by application of DEAE-Sepharose CL-6B chromatography as final step is described. This enzyme consists of five subunits of different molecular weight: alpha (65000), beta (55000),gamma (35000), delta (20000), and epsilon (17000). Disc electrophoresis on 5% polyacrylamide gels removes the epsilon-polypeptide yielding an active ATPase complex with four different subunits: alpha, beta, gamma, delta. Additionally, by variation of the ionic strength delta can (partly) removed allowing the isolation by disc electrophoresis of an active ATPase complex which consists only of three different subunits alpha, beta, and gamma. If the DEAE-Sepharose chromatography is carried out in the absence of diisopropyl phosphofluoridate (auto)proteolysis yields both an active ATPase with the subunits alpha+ (mol. wt 61000), beta, gamma, and delta and an inactive protein complex with the subunits alpha+, beta, gamma, delta, and two additional polypeptides a (mol. wt 38000) and b (mol. wt 23000). The latter two polypeptides are supposedly fragments of alpha+-chains which have become partially cleaved by (auto)proteolysis.