Magnetic Metal-Organic Framework Composite by Fast and Facile Mechanochemical Process.

Magnetic porous metal-organic framework nanocomposite was obtained by an easy, efficient, and environmentally friendly fabrication method. The material consists in magnetic spinel iron oxide nanoparticles incorporated in an iron(III) carboxylate framework. The magnetic composite was fabricated by a multistep mechanochemical approach. In the first step, iron oxide nanoparticles were obtained via ball milling inducing mechanochemical reaction between iron chlorides and NaOH using NaCl as dispersing agent. Magnetic nanoparticles (MNs) were functionalized by neat grinding with benzene-1,3,5-tricarboxylic acid (1, 3, 5 BTC) and were then subjected to liquid assisted milling using hydrated FeCl3, water, and ethanol to obtain a magnetic framework composite (MFC) consisting of iron oxide nanoparticles encapsulated in a MOF matrix. We report, for the first time, the applicability of the grinding method to obtain a magnetic composite of metal-organic frameworks. The synthesized material exhibits magnetic characteristics and high porosity, and it has been tested as carrier for targeted drug delivery studying loading and release of a model drug (doxorubicin). Developed systems can associate therapeutics and diagnostics properties with possible relevant impact for theranostic and personalized patient treatment. Furthermore, the material properties make them excellent candidates for several other applications such as catalysis, sensing, and selective sequestration processes.

The thiazole derivative CPTH6 impairs autophagy.

We have previously demonstrated that the thiazole derivative 3-methylcyclopentylidene-[4-(4'-chlorophenyl)thiazol-2-yl]hydrazone (CPTH6) induces apoptosis and cell cycle arrest in human leukemia cells. The aim of this study was to evaluate whether CPTH6 is able to affect autophagy. By using several human tumor cell lines with different origins we demonstrated that CPTH6 treatment induced, in a dose-dependent manner, a significant increase in autophagic features, as imaged by electron microscopy, immunoblotting analysis of membrane-bound form of microtubule-associated protein 1 light chain 3 (LC3B-II) levels and by appearance of typical LC3B-II-associated autophagosomal puncta. To gain insights into the molecular mechanisms of elevated markers of autophagy induced by CPTH6 treatment, we silenced the expression of several proteins acting at different steps of autophagy. We found that the effect of CPTH6 on autophagy developed through a noncanonical mechanism that did not require beclin-1-dependent nucleation, but involved Atg-7-mediated elongation of autophagosomal membranes. Strikingly, a combined treatment of CPTH6 with late-stage autophagy inhibitors, such as chloroquine and bafilomycin A1, demonstrates that under basal condition CPTH6 reduces autophagosome turnover through an impairment of their degradation pathway, rather than enhancing autophagosome formation, as confirmed by immunofluorescence experiments. According to these results, CPTH6-induced enhancement of autophagy substrate p62 and NBR1 protein levels confirms a blockage of autophagic cargo degradation. In addition, CPTH6 inhibited autophagosome maturation and compounds having high structural similarities with CPTH6 produced similar effects on the autophagic pathway. Finally, the evidence that CPTH6 treatment decreased α-tubulin acetylation and failed to increase autophagic markers in cells in which acetyltransferase ATAT1 expression was silenced indicates a possible role of α-tubulin acetylation in CPTH6-induced alteration in autophagy. Overall, CPTH6 could be a valuable agent for the treatment of cancer and should be further studied as a possible antineoplastic agent.

The state of the art of pyrazole derivatives as monoamine oxidase inhibitors and antidepressant/anticonvulsant agents.

Monoamine oxidase plays a significant role in the control of intracellular concentration of monoaminergic neurotransmitters or neuromodulators and dietary amines. The rapid degradation of these molecules ensures the proper functioning of synaptic neurotransmission and is critically important for the regulation of emotional and other brain functions. The development of human MAO inhibitors led to important breakthroughs in the therapy of several neuropsychiatric disorders. Different families of heterocycles containing 2 or 4 nitrogen atoms have been used as scaffolds for synthesizing selective monoamine oxidase inhibitors, but the early period of the MAO-inhibitors started with hydrazine derivatives. Pyrazole, pyrazoline, and pyrazolidine derivatives can be considered as a cyclic hydrazine moiety. This scaffold also displayed promising antidepressant and anticonvulsant properties as demonstrated by different and established animal models. Diversely substituted pyrazoles, embedded with a variety of functional groups, are important biological agents and a significant amount of research activity has been directed towards this chemical class.

Synthesis of new 3-aryl-4,5-dihydropyrazole-1-carbothioamide derivatives. An investigation on their ability to inhibit monoamine oxidase.

Some differently substituted 3-aryl-4,5-dihydropyrazoles-1-carbothioamides have been synthesised with the aim to investigate their monoamine oxidase inhibitory activity. The chemical structures of the compounds have been characterized by means of their IR, (1)H NMR, (13)C NMR spectroscopic data and elemental analyses. All the active compounds showed a selective activity towards the B isoform of the enzyme, regardless of the substitution on the heterocyclic ring. The inhibition of the enzymatic activity was measured on human recombinant MAO isoforms, expressed in baculovirus infected BTI insect cells. Docking experiments were carried out with the aim to rationalize the mechanism of inhibition of the most active and selective compound.

High-performance liquid chromatographic separation of enantiomers and diastereomers of 2-methylcyclohexanone thiosemicarbazone, and determination of absolute configuration and configurational stability.

Simultaneous HPLC diastereo- and enantioseparations of 2-methylcyclohexanone thiosemicarbazone (2-MCET) were accomplished on coated- and immobilized type polysaccharide-based chiral stationary phases (CSPs). The identification of all stereoisomeric forms and their stereochemistry were achieved by combining theoretical, HPLC and chiroptical data. The stereochemical stability of the target compound was studied by classical off-column and dynamic HPLC kinetic procedures and the influence of different parameters such solvent, TFA concentration and temperature on stereoisomerization process was evaluated. The findings obtained by chromatographic and kinetic experiments were used to develop a simple method to convert the racemic form of 2-MCET into a single enantiomer.

Analytical and semipreparative high performance liquid chromatography enantioseparation of new substituted 1-thiocarbamoyl-3,5-diaryl-4,5-dihydro-(1H)-pyrazoles on polysaccharide-based chiral stationary phases in normal-phase, polar organic and reversed-phase conditions.

The direct HPLC enantioseparation of five pairs of new chiral pyrazole derivatives on coated cellulose- and amylose-based chiral stationary phases (Chiralpak AD, Chiralcel OJ and Chiralcel OJ-RH) and new immobilised amylose-based Chiralpak IA CSP was performed. Very high enantioselectivity factor (alpha) values were achieved in polar organic and reversed-phase conditions by using OJ-RH as CSP. Chiralpak IA exhibited an excellent chiral resolving ability in normal-phase mode and it allowed the enantioseparation of analytes investigated with resolution factors (Rs) >20. Due to its bonded nature, it was successfully employed at analytical and semipreparative scale in combination with normal-phase eluents containing "non-standards" solvents such as acetone.

Synthesis and in vitro selective anti-Helicobacter pylori activity of pyrazoline derivatives.

In order to develop new anti-Helicobacter pylori agents, a series of N1-substituted 3,5-diphenyl pyrazolines P1-P13 was prepared and evaluated for their antibacterial activity. All synthesized compounds showed little or no activity against different species of Gram-positive and Gram-negative bacteria of clinical relevance and against various strains of pathogenic fungi. The same derivatives exhibited a significant degree of activity against a range of H. pylori strains, including those resistant to the reference compound metronidazole. Among the prepared compounds those with an N1-acetyl group and a 4-methoxy substituent in the 5-phenyl ring showed the best activity against H. pylori metronidazole resistant strains in the 1-4 microg/mL MIC range.

Efficacy of Hypericum and Calendula oils in the epithelial reconstruction of surgical wounds in childbirth with caesarean section.

Following studies on the properties of spontaneous plants in Sardinia we have evaluated the tissue regenerating action of a mixture of oily extracts of Hypericum perforatum and Calendula arvensis on surgical wounds from childbirth with caesarean section.

Synthesis and antimicrobial activity of coumarin 7-substituted cephalosporins and sulfones.

Some coumarin 7-substituted cephalosporins and related sulfones were prepared and an antimicrobial assay was performed. The minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) carried out on cephalosporins showed a potential activity of some of the synthesized compounds against Gram-positive microorganisms. The tests performed on the corresponding sulfones showed no significant activity, neither as antimicrobial agents nor as inhibitors of beta-lactamase. An association of sulfone 6a with ampicillin was observed to inhibit Gram-positive microorganisms with a lower MIC than for ampicillin alone.

Synthesis via carbon suboxide and pharmacological activity of coumarin derivatives.

This report sums up the research work since 1993 on the synthesis of coumarin derivatives using carbon suboxide as reagent.

Synthesis and anti-microbial activity of benzo-condensed heterocyclic derivatives.

The synthesis of 2,4-dione derivatives of 1,5-benzodithiepine, 1,5-benzodiazepine and 1,5-benzothiazepine and the anti-microbial activity in vitro of these derivatives and of analogous of 1,5-benzodioxepine, 1,5-benzoxathiepine and 1,5-benzoxazepine, previously prepared, are reported. Some of these compounds showed a good activity against some Gram positive microorganisms and blastomycetes.