Curcumin as scaffold for drug discovery against neurodegenerative diseases

Neurodegenerative diseases (NDs) are one of major public health problems and their impact is continuously growing. Curcumin has been proposed for the treatment of several of these pathologies, such as Alzheimer’s disease (AD) and Parkinson’s disease (PD) due to the ability of this molecule to reduce inflammation and aggregation of involved proteins. Nevertheless, the poor metabolic stability and bioavailability of curcumin reduce the possibilities of its practical use. For these reasons, many curcumin derivatives were synthetized in order to overcome some limitations. In this review will be highlighted recent results on modification of curcumin scaffold in the search of new effective therapeutic agents against NDs, with particular emphasis on AD

From Conventional to Sustainable Catalytic Approaches for Heterocycles Synthesis

Synthesis of heterocyclic compounds is fundamental for all the research area in chemistry, from drug synthesis to material science. In this framework, catalysed synthetic methods are of great interest to effective reach such important building blocks. In this review, we will report on some selected examples from the last five years, of the major improvement in the field, focusing on the most important conventional catalytic systems, such as transition metals, organocatalysts, to more sustainable ones such as photocatalysts, iodine-catalysed reaction, electrochemical reactions and green innovative methods.Catalysed synthetic methods, such as transition metals, organocatalysts, photocatalysts, iodine-catalysed reaction, electrochemical reactions and green innovative methods are of great interest for the sustainable synthesis of heterocyclic compounds, important building blocks for several applications.imag

Shaping 1,2,4-Triazolium Fluorinated Ionic Liquid Crystals

The synthesis and thermotropic behaviour of some di-alkyloxy-phenyl-1,2,4-triazolium trifluoromethane-sulfonate salts bearing a seven-carbon atom perfluoroalkyl chain on the cation is herein described. The fluorinated salts presenting a 1,2,4-triazole as a core and differing in the length of two alkyloxy chains on the phenyl ring demonstrated a typical liquid crystalline behaviour. The mesomorphic properties of this set of salts were studied by differential scanning calorimetry and polarized optical microscopy. The thermotropic properties are discussed on the grounds of the tuneable structures of the salts. The results showed the existence of a monotropic, columnar, liquid crystalline phase for the salts tested. An increase in the temperature mesophase range and the presence of two enantiotropic mesophases for the sixteen-atom alkyloxy chain salt can be observed by increasing the length of the alkyloxy chain on the phenyl ring

Ammonium formate-Pd/C as a new reducing system for 1,2,4-oxadiazoles. Synthesis of guanidine derivatives and reductive rearrangement to quinazolin-4-ones with potential anti-diabetic activity

1,2,4-Oxadiazole is a heterocycle with wide reactivity and many useful applications. The reactive O-N bond is usually reduced using molecular hydrogen to obtain amidine derivatives. NH4 CO2 H-Pd/C is here demonstrated as a new system for the O-N reduction, allowing us to obtain differently substituted acylamidine, acylguanidine and diacylguanidine derivatives. The proposed system is also effective for the achievement of a reductive rearrangement of 5-(2′-aminophenyl)-1,2,4-oxadiazoles into 1-alkylquinazolin-4(1H)-ones. The alkaloid glycosine was also obtained with this method. The obtained compounds were preliminarily tested for their biological activity in terms of their cytotoxicity, induced oxidative stress, α-glucosidase and DPP4 inhibition, showing potential application as anti-diabetics

Synthesis of oxazolidinones from N-aryl-carbamate and epichlorohydrin under mild conditions

The reaction conditions for an enantiospecific synthesis of various N-aryl-oxazolidinones from N-aryl-carbamates and (R) or (S) epichlorohydrin were optimized. The N-aryl-oxazolidinones were applied to the synthesis of compounds of biological interest such as DuP 721, toloxatone and a linezolid analogue

FDA-Approved Fluorinated Heterocyclic Drugs from 2016 to 2022

The inclusion of fluorine atoms or heterocyclic moiety into drug structures represents a recurrent motif in medicinal chemistry. The combination of these two features is constantly appearing in new molecular entities with various biological activities. This is demonstrated by the increasing number of newly synthesized fluorinated heterocyclic compounds among the Food and Drug Administration FDA-approved drugs. In this review, the biological activity, as well as the synthetic aspects, of 33 recently FDA-approved fluorinated heterocyclic drugs from 2016 to 2022 are highlighted

Effects of Autologous Microfragmented Adipose Tissue on Healing of Tibial Plateau Levelling Osteotomies in Dogs: A Prospective Clinical Trial

The aim of this study was to evaluate the effects of autologous microfragmented adipose tissue (MFAT) applied after mechanical fragmentation and assess these effects radiographically in bone healing in dogs subjected to tibial plateau levelling osteotomy (TPLO). Twenty dogs with unilateral cranial cruciate ligament disease were enrolled and randomly assigned to the treatment group (MFAT) or the control group (NT). The MFAT group underwent TPLO and autologous MFAT intra-articular administration, while the NT group underwent TPLO alone. Adipose tissue was collected from the thigh region, and MFAT was obtained by mechanical fragmentation at the end of the surgery. The patients were subjected to X-ray examination preoperatively, immediately postoperatively (T0), and at 4 (T1) and 8 (T2) weeks postoperatively. Two radiographic scores that had previously been described for the evaluation of bone healing after TPLO were used. A 12-point scoring system (from 0 = no healing to 12 = complete remodelling) was used at T0, T1, and T2, while a 5-point scoring system (from 0 = no healing to 4 = 76–100% of healing) was used at T1 and T2. The median healing scores were significantly higher at T1 and T2 for the MFAT group compared with the NT group for the 12-point (p < 0.05) and 5-point (p < 0.05) scoring systems. The intra-articular injection of autologous microfragmented adipose tissue can accelerate bone healing after TPLO without complication

Multicomponent Synthesis of Benzothiophen-2-acetic Esters by a Palladium Iodide Catalyzed S-cyclization – Alkoxycarbonylation Sequence

A catalytic carbonylative approach to the multicomponent synthesis of benzothiophene derivatives from simple building blocks [1-(2-(methylthio)phenyl)prop-2-yn-1-ols, carbon monoxide, and an alcohol)] is presented. It is based on an S-cyclization-demethylation-alkoxycarbonylation-reduction sequence promoted by the PdI2/KI catalytic system, occurring under relatively mild conditions (40 atm, 80 °C, 15 h). Benzothiophene-2-acetic esters are obtained in moderate to good yields (35–70%) starting from variously substituted substrates in combination with different alcohols as external nucleophiles (17 examples). (Figure presented.)

Ultrasonographic measurements of abdominal lymph nodes in growing puppies

The sonographic appearance of the normal abdominal lymph nodes in adult dogs has been well described, but the data in puppies are scarce and of poor quality. The aim of the current study was to evaluate any differences in abdominal lymph node sonographic measurements in puppies of various sizes and to determine whether any differences were correlated with growth and weight gain during the first 10 weeks of life. By an approach based on prospective and serial measurements, length, width and thickness of jejunal, medial iliac and hypogastric nodes were obtained in twenty-one healthy puppies of various sizes, at six (T0), eight (T1) and ten (T2) weeks of age. The relationship between body weight and length, width and thickness of lymph nodes was evaluated using a Pearson correlation analysis. An ANOVA test was used to compare the measurements at different ages. Jejunal and iliac lymph nodes were the largest in large breed dogs. In large-sized puppies only the length of the jejunal lymph nodes correlated positively with width and body weight. Length of medial iliac lymph nodes correlated positively with width and body weight in all three sizes. None of the measurements of hypogastric lymph nodes were related to body weight. In large-sized puppies jejunal and iliac lymph nodes increased in length and width with age; in medium-sized puppies only iliac lymph nodes increased; in small-sized puppies jejunal and iliac lymph nodes significantly decreased in length and thickness. In conclusion, the lymph node sizes in young animals are directly related to body weight and do not decrease with growth during the first 10 weeks of life, except in small-sized puppies