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

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

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

Curcumin affects HSP60 folding activity and levels in neuroblastoma cells

The fundamental challenge in fighting cancer is the development of protective agents able to interfere with the classical pathways of malignant transformation, such as extracellular matrix remodeling, epithelial\u2013mesenchymal transition and, alteration of protein homeostasis. In the tumors of the brain, proteotoxic stress represents one of the main triggering agents for cell transformation. Curcumin is a natural compound with anti-inflammatory and anti-cancer properties with promising potential for the development of therapeutic drugs for the treatment of cancer as well as neurodegenerative diseases. Among the mediators of cancer development, HSP60 is a key factor for the maintenance of protein homeostasis and cell survival. High HSP60 levels were correlated, in particular, with cancer development and progression, and for this reason, we investigated the ability of curcumin to affect HSP60 expression, localization, and post-translational modifications using a neuroblastoma cell line. We have also looked at the ability of curcumin to interfere with the HSP60/HSP10 folding machinery. The cells were treated with 6, 12.5, and 25 \ub5M of curcumin for 24 h, and the flow cytometry analysis showed that the compound induced apoptosis in a dose-dependent manner with a higher percentage of apoptotic cells at 25 \ub5M. This dose of curcumin-induced a decrease in HSP60 protein levels and an upregulation of HSP60 mRNA expression. Moreover, 25 \ub5M of curcumin reduced HSP60 ubiquitination and nitration, and the chaperonin levels were higher in the culture media compared with the untreated cells. Furthermore, curcumin at the same dose was able to favor HSP60 folding activity. The reduction of HSP60 levels, together with the increase in its folding activity and the secretion in the media led to the supposition that curcumin might interfere with cancer progression with a protective mechanism involving the chaperonin