Design, synthesis and biological activity of selective hCAs inhibitors based on 2-(benzylsulfinyl)benzoic acid scaffold

A large library of derivatives based on the scaffold of 2-(benzylsulfinyl)benzoic acid were synthesised and tested as atypical inhibitors against four different isoforms of human carbonic anhydrase (hCA I, II, IX and XII, EC 4.2.1.1). The exploration of the chemical space around the main functional groups led to the discovery of selective hCA IX inhibitors in the micromolar/nanomolar range, thus establishing robust structure-activity relationships within this versatile scaffold. HPLC separation of some selected chiral compounds and biological evaluation of the corresponding enantiomers was performed along with molecular modelling studies on the most active derivatives

Mealworm (Tenebrio molitor): Potential and challenges to promote circular economy

Over the last few years, the concept of Circular Economy (CE) has received a lot of atten-tion due to its potential contribution to the Sustainable Development Goals (SDGs), especially by reconciling economic growth with the protection of the environment through its grow-make-use-restore approach. The use of insects in circular production systems has been a good example of this concept as insects can transform a wide range of organic waste and by-products into nutritious feedstuffs, which then go back into the production cycle. This paper explores the potential of meal-worms (Tenebrio molitor) in circular production systems by reviewing their use and applicability in several industries such as pharmaceuticals, agriculture, food, etc. Despite the high versatility of this insect and its potential as a substitute source of nutrients and other valuable components, there are still many legislative and behavioural challenges that hinder its adoption and acceptance

Selective inhibition of carbonic anhydrase IX and XII by coumarin and psoralen derivatives

A small library of coumarin and their psoralen analogues EMAC10157a-b-d-g and EMAC10160a-b-d-g has been designed and synthesised to investigate the effect of structural modifications on their inhibition ability and selectivity profile towards carbonic anhydrase isoforms I, II, IX, and XII. None of the new compounds exhibited activity towards hCA I and II isozymes. Conversely, both coumarin and psoralen derivatives were active against tumour associated isoforms IX and XII in the low micromolar or nanomolar range of concentration. These data further corroborate our previous findings on analogous derivatives, confirming that both coumarins and psoralens are interesting scaffolds for the design of isozyme selective hCA inhibitors

Continuous-Flow Synthesis of Arylthio-Cyclopropyl Carbonyl Compounds

The straightforward, continuous-flow synthesis of cyclopropyl carbaldehydes and ketones has been developed starting from 2-hydroxycyclobutanones and aryl thiols. This acid-catalyzed mediated procedure allows access to the multigram and easily scalable synthesis of cyclopropyl adducts under mild conditions, using reusable Amberlyst-35 as a catalyst. The resins, suitably ground and used for filling steel columns, have been characterized via TGA, ATR, SEM and BET analyses to describe the physical-chemical properties of the packed bed and the continuous-flow system in detail. To highlight the synthetic versatility of the arylthiocyclopropyl carbonyl compounds, a series of selective oxidation reactions have been performed to access sulfoxide and sulfone carbaldehyde cyclopropanes, oxiranes and carboxylic acid derivatives

Morbid obesity in a young woman affected by advanced chronic kidney disease: an exceptional case report. Does a high dose of essential amino acids play a key role in therapeutic success?

A 38-year-old woman, obese (219\u2009kg), diabetic, hypertensive, chronic kidney disease (CKD) stage 4, with low plasma albumin level (2.9\u2009g\u2009dl(-1)) and marked proteinuria (22\u2009g per day) was studied. Given the advanced-stage CKD with nephrotic proteinuria, we supplemented low-protein diet with high doses of a tailored essential amino acid mixture (AAs: 44\u2009g per day) to improve weight reduction in the patient. After 20 months of conservative therapy, the patient lost 43\u2009kg; despite two episodes of infection, albumin plasma levels increased up to 3.7\u2009g per day. After a further 20 months of dialysis, the patient maintained a diet of 1800 kcal supplemented with 32\u2009g of AAs and lost 47\u2009kg, whereas both albumin (3.89\ub10.12\u2009g\u2009dl(-1)) and C reactive protein returned to normal. During the follow-up period, anemia improved, erythropoietin was thus discontinued and insulin requirement decreased to 105 IU. This therapeutic option may be beneficial in advanced CKD patients with obesity and diabetes resulting from malnutrition

Effects of Dietary Supplementation with Honeybee Pollen and Its Supercritical Fluid Extract on Immune Response and Fillet’s Quality of Farmed Gilthead Seabream (Sparus aurata)

The awareness of the correlation between administered diet, fish health and products’ quality has led to the increase in the research for innovative and functional feed ingredients. Herein, a plant-derived product rich in bioactive compounds, such as honeybee pollen (HBP), was included as raw (HBP) and as Supercritical Fluid Extracted (SFE) pollen (HBP_SFE) in the diet for gilthead seabream (Sparus aurata). The experiment was carried out on 90 fish with an average body weight of 294.7 ± 12.8 g, divided into five groups, according to the administration of five diets for 30 days: control diet (CTR); two diets containing HBP at 5% (P5) and at 10% (P10) level of inclusion; two diets containing HBP_SFE, at 0.5% (E0.5) and at 1% (E1) level of inclusion. Their effects were evaluated on 60 specimens (336.2 ± 11.4 g average final body weight) considering the fish growth, the expression of some hepatic genes involved in the inflammatory response (il-1β, il-6 and il-8) through quantitative real-time PCR, and physico-chemical characterization (namely color, texture, water holding capacity, fatty acid profile and lipid peroxidation) of the fish fillets monitored at the beginning (day 0) and after 110 days of storage at −20◦C. The results obtained showed that the treatment with diet E1 determined the up-regulation of il-1β, il-6, and il-8 (p < 0.05); however, this supplementation did not significantly contribute to limiting the oxidative stress. Nevertheless, no detrimental effect on color and the other physical characteristics was observed. These results suggest that a low level of HBP_SFE could be potentially utilized in aquaculture as an immunostimulant more than an antioxidant, but further investigation is necessary

Mucuna pruriens (Velvet bean) Rescues Motor, Olfactory, Mitochondrial and Synaptic Impairment in PINK1(B9) Drosophila melanogaster Genetic Model of Parkinson's Disease

The fruit fly Drosophila melanogaster (Dm) mutant for PTEN-induced putative kinase 1 (PINK1B9) gene is a powerful tool to investigate physiopathology of Parkinson's disease (PD). Using PINK1B9 mutant Dm we sought to explore the effects of Mucuna pruriens methanolic extract (Mpe), a L-Dopa-containing herbal remedy of PD. The effects of Mpe on PINK1B9 mutants, supplied with standard diet to larvae and adults, were assayed on 3–6 (I), 10–15 (II) and 20–25 (III) days old flies. Mpe 0.1% significantly extended lifespan of PINK1B9 and fully rescued olfactory response to 1-hexanol and improved climbing behavior of PINK1B9 of all ages; in contrast, L-Dopa (0.01%, percentage at which it is present in Mpe 0.1%) ameliorated climbing of only PINK1B9 flies of age step II. Transmission electron microscopy analysis of antennal lobes and thoracic ganglia of PINK1B9 revealed that Mpe restored to wild type (WT) levels both T-bars and damaged mitochondria. Western blot analysis of whole brain showed that Mpe, but not L-Dopa on its own, restored bruchpilot (BRP) and tyrosine hydroxylase (TH) expression to age-matched WT control levels. These results highlight multiple sites of action of Mpe, suggesting that its effects cannot only depend upon its L-Dopa content and support the clinical observation of Mpe as an effective medication with intrinsic ability of delaying the onset of chronic L-Dopa-induced long-term motor complications. Overall, this study strengthens the relevance of using PINK1B9 Dm as a translational model to study the properties of Mucuna pruriens for PD treatment

Synthesis and evaluation of thymol-based synthetic derivatives as dual-action inhibitors against different strains of h. pylori and AGS cell line

Following a similar approach on carvacrol-based derivatives, we investigated the synthesis and the microbiological screening against eight strains of H. pylori, and the cytotoxic activity against human gastric adenocarcinoma (AGS) cells of a new series of ether compounds based on the structure of thymol. Structural analysis comprehended elemental analysis and 1H/13C/19F NMR spectra. The analysis of structure-activity relationships within this molecular library of 38 structurally-related compounds reported that some chemical modifications of the OH group of thymol led to broad-spectrum growth inhibition on all isolates. Preferred substitutions were benzyl groups compared to alkyl chains, and the specific presence of functional groups at para position of the benzyl moiety such as 4-CN and 4-Ph endowed the most anti-H. pylori activity toward all the strains with minimum inhibitory concentration (MIC) values up to 4 µg/mL. Poly-substitution on the benzyl ring was not essential. Moreover, several compounds characterized by the lowest minimum inhibitory concentration/minimum bactericidal concentration (MIC/MBC) values against H. pylori were also tested in order to verify a cytotoxic effect against AGS cells with respect to 5-fluorouracil and carvacrol. Three derivatives can be considered as new lead compounds alternative to current therapy to manage H. pylori infection, preventing the occurrence of severe gastric diseases. The present work confirms the possibility to use natural compounds as templates for the medicinal semi-synthesis

The quest for companions to post-common envelope binaries: I. Searching a sample of stars from the CSS and SDSS

As part of an ongoing collaboration between student groups at high schools and professional astronomers, we have searched for the presence of circum-binary planets in a bona-fide unbiased sample of twelve post-common envelope binaries (PCEBs) from the Catalina Sky Survey (CSS) and the Sloan Digital Sky Survey (SDSS). Although the present ephemerides are significantly more accurate than previous ones, we find no clear evidence for orbital period variations between 2005 and 2011 or during the 2011 observing season. The sparse long-term coverage still permits O-C variations with a period of years and an amplitude of tens of seconds, as found in other systems. Our observations provide the basis for future inferences about the frequency with which planet-sized or brown-dwarf companions have either formed in these evolved systems or survived the common envelope (CE) phase.Comment: accepted by A&