New bioactive hydrogenated linderazulene-derivatives from the gorgonian Echinogorgia complexa

Chemical analysis of the secondary metabolite pattern of the gorgonian Echinogorgia complexa, collected along South Indian coasts, showed the presence of two new tricyclic guaiane furanosesquiterpenes, iso-echinofuran (3) and 8,9-dihydro-linderazulene (4), co-occurring with the known echinofuran (5) and structurally related to the pigment linderazulene (1). The unprecedented molecules 3 and 4 were characterized by spectral methods, mainly by NMR techniques. Compounds 3-5 displayed moderate activity in the mitochondrial respiratory chain inhibition assay.     

fac-{Ru(CO)3}2+-core complexes and design of metal-based drugs. synthesis, structure, and reactivity of Ru-thiazole derivative with serum proteins and absorption-release studies with acryloyl and silica hydrogels as carriers in physiological media

The reaction of [Ru2(CO)6Cl4], 1, with excess THZ (1,3-thiazole) in absolute ethanol at 55 degrees C produces fac-[Ru(CO)3Cl2(THZ)], 2, in high yield. [Ru(CO)2Cl2(THZ)2], 3, is formed at higher temperature (ca 70 degrees C) and higher concentration of THZ. The X-ray structures of the new compounds have been determined, and density functional studies performed at the hybrid B3LYP/(Lanl2DZ, Ru; 6-311+G**, CHClNOS) level allowed the estimation of the structures of several conformers as well as that of their relative total electronic energies. Compound 2 is soluble (slowly) in aqueous media, where it reacts with the transport proteins bovine serum albumin (BSA) and human apotransferrin (HTF), and at a lower extent with calf thymus DNA (CT-DNA) and with guanosine-5'-monophosphate (GMP). The complex molecule is adsorbed by certain synthetic acryloyl polymers that have terminal carboxylate functions and is embedded in silica gels when these latter are prepared in the presence of a solution of 2. Ruthenium species are slowly released from the loaded gels into physiological solutions at pH 7.4. The reactivity of 2 with biomolecules and synthetic hydrogels makes it a compound of interest for anticancer and antimetastases tests.     

Bisphosphonate complexation and calcium doping in silica xerogels as a combined strategy for local and controlled release of active platinum antitumor compounds

The production of bone substitute biomimetic materials which could also act as antitumoral drug release agents is of enormous interest. We report in this paper the synthesis and characterization of a novel platinum dinuclear complex containing a geminal bisphosphonate and its embodiment into xerogels prepared by the sol-gel method. Our goal was to obtain a hybrid inorganic matrix that could release a platinum species active against bone tumors or metastases, upon local implant. Two silica xerogels were considered: one was composed of pure silica, while the other contained also some calcium as potential release-modulating agent thanks to its high affinity for bisphophonates. The platinum-complex loading capacity of the inorganic matrices, the release kinetics in buffer simulating physiological conditions, and the stability upon storage were investigated as a function of Pt-complex concentration and calcium addition. We found that the presence of calcium in the composites deeply influences not only the stability of the formulations but also the nature of the platinum complex liberated in solution.     

Dimerization and polymerization of isoprene at high pressures

The high-pressure reactivity of isoprene has been studied at room temperature up to 2.6 GPa by using the diamond anvil cell technique in combination with Fourier transform infrared spectroscopy. Both dimerization and polymerization reactions take place above 1.1 GPa. At this pressure, the two processes are well separated in time, the dimerization being the only one occurring in the first 150 h. Both processes simultaneously occur as the pressure increases. The reaction product is composed of a volatile fraction, identified as sylvestrene, and a transparent rubberlike solid formed by cis-1,4- and 3,4-polyisoprene. The activation volume of the dimerization reaction has been obtained from the kinetic data. The photoinduced reaction, studied at room temperature for two different pressures, takes place through a two-photon absorption process, and the threshold pressure is lowered to 0.5 GPa. At this pressure, both the dimerization and polymerization processes occur, but the dimerization is not as selective as in the purely pressure-induced reaction. 4-Ethenyl-2,4-dimethylcyclohexene is obtained in addition to sylvestrene. By increasing the pressure, the photoinduced reaction becomes more selective, and the monomer is quantitatively transformed into the same polymer obtained in the purely pressure-induced reaction.     

Polyketide synthases and nonribosomal peptide synthetases: the emerging view from bacterial genomics

A total of 223 complete bacterial genomes are analyzed, with 281 citations, for the presence of genes encoding modular polyketide synthases (PKS) and nonribosomal peptide synthetases (NRPS). We report on the distribution of these systems in different bacterial taxa and, whenever known, the metabolites they synthesize. We also highlight, in the different bacterial lineages, the PKS and NRPS genes and, whenever known, the corresponding products.     

First synthesis of parazoanthine-A and its O-Me derivative

Parazoanthine A (7.0% overall yield) and its O-methyl derivative (6.2% overall yield) were prepared by a concise biomimetic synthesis based on the coupling reaction of l-arginine methyl ester dihydrochloride with isocyanate derivatives of p-coumaric acid and 4-methoxy-cinnamic acid, respectively. The synthetic approach is designed to obtain a wider class of parazoanthine analogs.     

Metal-Free Deoxygenation of Chiral Nitroalkanes: An Easy Entry to α-Substituted Enantiomerically Enriched Nitriles

A metal-free, mild and chemodivergent transformation involving nitroalkanes has been developed. Under optimized reaction conditions, in the presence of trichlorosilane and a tertiary amine, aliphatic nitroalkanes were selectively converted into amines or nitriles. Furthermore, when chiral β-substituted nitro compounds were reacted, the stereochemical integrity of the stereocenter was maintained and α-functionalized nitriles were obtained with no loss of enantiomeric excess. The methodology was successfully applied to the synthesis of chiral β-cyano esters, α-aryl alkylnitriles, and TBS-protected cyanohydrins, including direct precursors of four active pharmaceutical ingredients (ibuprofen, tembamide, aegeline and denopamine).     

Bioactive Compounds from Lemon (Citrus limon) Extract Overcome TNF-α-Induced Insulin Resistance in Cultured Adipocytes

The consumption of plant-based food is important for health promotion, especially regarding the prevention and management of chronic diseases such as diabetes. We investigated the effects of a lemon extract (LE), containing ≥20.0% total flavanones and ≥1.0% total hydroxycinnamic acids, on insulin signaling in murine 3T3-L1 adipocytes treated with TNF-α, which was used to mimic in vitro the insulin resistance condition that characterizes diabetes mellitus. Our results showed LE increased PPARγ, GLUT4 and DGAT-1 levels, demonstrating the potential of this lemon extract in the management of insulin resistance conditions associated with TNF-α pathway activation. LE treatment further decreased the release of interleukin 6 (IL-6) and restored triglyceride synthesis, which is the main feature of a healthy adipocyte.     

Chiral Supramolecular Switches Based on (R)‐Binaphthalene–Bipyridinium Guests and Cucurbituril Hosts

We designed and synthesized the three molecular tweezers 1 a – c ⁴⁺ containing an electron acceptor 4,4′‐bipyridinium (BPY²⁺) unit in each of the two arms and an (R)‐2,2′‐dioxy‐1,1′‐binaphthyl (BIN) unit that plays the role of chiral centre and the hinge of the structure. Each BPY²⁺ unit is connected to the BIN hinge by an alkyl chain formed by two‐ ( 1 a ⁴⁺), four‐ ( 1 b ⁴⁺), or six‐CH₂ ( 1 c ⁴⁺) groups. The behavior of 1 a – c ⁴⁺ upon chemical or photochemical reduction in the absence and in the presence of cucurbit[8]uril (CB[8]) or cucurbit[7]uril (CB[7]) as macrocyclic hosts for the bipyridinium units has been studied in aqueous solution. A detailed analysis of the UV/Vis absorption and circular dichroism (CD) spectra shows that the helicity of the BIN unit can be reversibly modulated by reduction of the BPY²⁺ units, or by association with cucurbiturils. Upon reduction of 1 a – c ⁴⁺ compounds, the formed BPY^{+ .} units undergo intramolecular dimerization with a concomitant change in the BIN dihedral angle, which depends on the length of the alkyl spacers. The alkyl linkers also play an important role in association to cucurbiturils. Compound 1 a ⁴⁺, because of its short carbon chain, associates to the bulky CB[8] in a 1:1 ratio, whereas in the case of the smaller host compound CB[7] a 1:2 complex is obtained. Compounds 1 b ⁴⁺ and 1 c ⁴⁺, which have longer linkers, associate to two cucurbiturils regardless of their sizes. In all cases, association with CB[8] causes an increase of the BIN dihedral angle, whereas the formation of CB[7] complexes causes an angle decrease. Reduction of the CB[8] complexes results in an enhancement of the BPY^{+ .} dimerization with respect to free 1 a – c ⁴⁺ and causes a noticeable decrease of the BIN dihedral angle, because the BPY^{+ .} units of the two arms have to enter into the same macrocycle. The dimer formation in the CB[8] complexes characterized by a 1:2 ratio implies the release of one macrocycle showing that the binding stoichiometry of these host–guest complexes can be switched from 1:2 to 1:1 by changing the redox state of the guest. When the reduction is performed on the CB[7] complexes, dimer formation is totally inhibited, as expected because the CB[7] cavity cannot host two BPY^{+ .} units.