Halo complexes of gold(I) containing glycoconjugate carbene ligands: synthesis, characterization, cytotoxicity and interaction with proteins and DNA model systems.

New neutral carbene complexes of gold(I) [Au(Im-Me)X] (X = Cl, Au1; X = Br, Au2; X = I, Au3) have been synthesized and fully characterized by different techniques, including NMR and UV-vis absorption spectroscopy and single crystal X-ray diffraction. The carbene ligand Im-Me is decorated with a glucoside fragment via a triazole linker, obtainable through a click chemistry reaction. The compounds retain the Au-NHC fragment in aqueous solvents, and an equilibrium between the neutral halo- and the cationic di-carbene form [Au(Im-Me)2]+ is observed, whose extent follows the trend Au1 < Au2 < Au3. Cytotoxicity studies on two cancer and two non-tumorigenic cell lines reflect the solution behavior, as a certain difference among the complexes was disclosed, with the iodo complex Au3 being more active and selective. The compounds interact with both DNA and protein model systems. The X-ray structure of the adduct formed upon the reaction of Au1 with bovine pancreatic ribonuclease (RNase A) reveals Au binding at the side chain of His105 of both protein molecules A and B of the asymmetric unit. The binding of gold atoms at both the nitrogen atoms of the imidazole ring of His15 and at the N-terminal tail has been found in the adduct formed with hen egg white lysozyme.

Isolation and Biological Characterization of Homoisoflavanoids and the Alkylamide N-p-Coumaroyltyramine from Crinum biflorum Rottb., an Amaryllidaceae Species Collected in Senegal.

Crinum biflorum Rottb. (syn. Crinum distichum) is an Amaryllidaceae plant used in African traditional medicine but very few studies have been performed on this species from a chemical and applicative point of view. Bulbs of C. biflorum, collected in Senegal, were extracted with ethanol by Soxhlet and the corresponding organic extract was purified using chromatographic methods. The pure compounds were chemically characterized by spectroscopic techniques (1D and 2D 1H and 13C NMR, HR MS and ECD) and X-ray analysis. Four homoisoflavonoids (1-4) and one alkylamide (5) were isolated and characterized as 5,6,7-trimethoxy-3-(4-hydroxybenzyl)chroman-4-one (1), as 3-hydroxy-5,6,7-trimethoxy-3-(4-hydroxybenzyl)chroman-4-one (2), as 3-hydroxy-5,6,7-trimethoxy-3-(4-methoxybenzyl)chroman-4-one (3) and as 5,6,7-trimethoxy-3-(4-methoxybenzyl)chroman-4-one (4), and the alkylamide as (E)-N-(4-hydroxyphenethyl)-3-(4-hydroxyphenyl)acrylamide (5), commonly named N-p-coumaroyltyramine. The relative configuration of compound 1 was verified thanks to the X-ray analysis which also allowed us to confirm its racemic nature. The absolute configurations of compounds 2 and 3 were assigned by comparing their ECD spectra with those previously reported for urgineanins A and B. Flavanoids 1, 3 and 4 showed promising anticancer properties being cytotoxic at low micromolar concentrations towards HeLa and A431 human cancer cell lines. The N-p-coumaroyltyramine (5) was selectively toxic to A431 and HeLa cancer cells while it protected immortalized HaCaT cells against oxidative stress induced by hydrogen peroxide. Compounds 1-4 also inhibited acetylcholinesterase activity with compound 3 being the most potent. The anti-amylase and the strong anti-glucosidase activity of compound 5 were confirmed. Our results show that C. biflorum produces compounds of therapeutic interest with anti-diabetic, anti-tumoral and anti-acetylcholinesterase properties.

Pt(II) versus Pt(IV) in Carbene Glycoconjugate Antitumor Agents: Minimal Structural Variations and Great Performance Changes.

Octahedral Pt(IV) complexes (2Pt-R) containing a glycoconjugate carbene ligand were prepared and fully characterized. These complexes are structural analogues to the trigonal bipyramidal Pt(II) species (1Pt-R) recently described. Thus, an unprecedented direct comparison between the biological properties of Pt compounds with different oxidation states and almost indistinguishable structural features was performed. The stability profile of the novel Pt(IV) compounds in reference solvents was determined and compared to that of the analogous Pt(II) complexes. The uptake and antiproliferative activities of 2Pt-R and 1Pt-R were evaluated on the same panel of cell lines. DNA and protein binding properties were assessed using human serum albumin, the model protein hen egg white lysozyme, and double stranded DNA model systems by a variety of experimental techniques, including UV-vis absorption spectroscopy, fluorescence, circular dichroism, and electrospray ionization mass spectrometry. Although the compounds present similar structures, their in-solution stability, cellular uptake, and DNA binding properties are diverse. These differences may represent the basis of their different cytotoxicity and biological activity.

Crystal structures of butyl 2-amino-5-hy-droxy-4-(4-nitro-phen-yl)benzo-furan-3-carboxyl-ate and 2-meth-oxy-ethyl 2-amino-5-hy-droxy-4-(4-nitro-phen-yl)benzo-furan-3-carboxyl-ate.

The title benzo-furan derivatives 2-amino-5-hy-droxy-4-(4-nitro-phen-yl)benzo-furan-3-carboxyl-ate (BF1), C19H18N2O6, and 2-meth-oxy-ethyl 2-amino-5-hy-droxy-4-(4-nitro-phen-yl)benzo-furan-3-carboxyl-ate (BF2), C18H16N2O7, recently attracted attention because of their promising anti-tumoral activity. BF1 crystallizes in the space group P . BF2 in the space group P21/c. The nitro-phenyl group is inclined to benzo-furan moiety with a dihedral angle between their mean planes of 69.2 (2)° in BF1 and 60.20 (6)° in BF2. A common feature in the mol-ecular structures of BF1 and BF2 is the intra-molecular N-H⋯Ocarbon-yl hydrogen bond. In the crystal of BF1, the mol-ecules are linked head-to-tail into a one-dimensional hydrogen-bonding pattern along the a-axis direction. In BF2, pairs of head-to-tail hydrogen-bonded chains of mol-ecules along the b-axis direction are linked by O-H⋯Ometh-oxy hydrogen bonds. In BF1, the butyl group is disordered over two orientations with occupancies of 0.557 (13) and 0.443 (13).

A highly efficient and selective antitumor agent based on a glucoconjugated carbene platinum(ii) complex.

New five-coordinate Pt(ii) complexes containing a glycosylated carbene fragment were synthesized. A member of this class shows very high in vitro cytotoxicity and an exceptional selectivity toward malignant cells. The complex lacking the sugary portion fails in the recognition of cancer cells. The results support the use of glycosylation in the design of carbene Pt-based anticancer agents.

Data on a real-time tripodal colorimetric/fluorescence sensor for multiple target metal ions.

Currently considerable research both in life and in environmental sciences is dedicated to chemosensors able to detect metals of biological interest such as zinc and iron or other toxic and carcinogenic, as cadmium, mercury, chromium, lead. Recently, a new chemosensor strategy of "single chemosensor for multiple metals" has emerged. For this scope, many fluorescent sensors for Cd(II) and Zn(II) have been designed and synthetized, as ligand systems or in polymeric matrices [1], [2], [3]. The data presented in this article include experimental data on the of a pyridyl/phenolic/benzothiazole functionalized colorimetric receptor (BPAP) and its selectively recognise Fe(III) and Fe(II) ions with visible, naked eye colour changes and fluorometric selectivity towards Zn2+ and Cd2+ ions in aqueous medium. This article is submitted as a companion paper to Caruso et al. (2018) [4].

Crystal structure of N,N'-bis-(2,4-di-fluoro-benzo-yloxy)benzene-1,2:4,5-tetra-carboximide.

Mol-ecules of the title compound, C24H8F4N2O8, have Ci point-group symmetry in the crystal, as they lie on crystallographic inversion centres (Z' = 1/2). The di-fluoro-phenyl ring is disordered over two orientations; the final refined occupancy factors of the two components of disorder are 0.947 (4) and 0.053 (4). In the crystal, some Car-H⋯F inter-actions are present, which involve the most acidic H atom of the mol-ecule.

Higginsianins A and B, Two Diterpenoid α-Pyrones Produced by Colletotrichum higginsianum, with in Vitro Cytostatic Activity.

Two new diterpenoid α-pyrones, named higginsianins A (1) and B (2), were isolated from the mycelium of the fungus Colletotrichum higginsianum grown in liquid culture. They were characterized as 3-[5a,9b-dimethyl-7-methylene-2-(2-methylpropenyl)dodecahydronaphtho[2,1-b]furan-6-ylmethyl]-4-hydroxy-5,6-dimethylpyran-2-one and 4-hydroxy-3-[6-hydroxy-5,8a-dimethyl-2-methylene-5-(4-methylpent-3-enyl)decahydronaphthalen-1-ylmethyl]-5,6-dimethylpyran-2-one, respectively, by using NMR, HRESIMS, and chemical methods. The structure and relative configuration of higginsianin A (1) were confirmed by X-ray diffractometric analysis, while its absolute configuration was assigned by electronic circular dichroism (ECD) experiments and calculations using a solid-state ECD/TDDFT method. The relative and absolute configuration of higginsianin B (2), which did not afford crystals suitable for X-ray analysis, were determined by NMR analysis and by ECD in comparison with higginsianin A. 1 and 2 were the C-8 epimers of subglutinol A and diterpenoid BR-050, respectively. The evaluation of 1 and 2 for antiproliferative activity against a panel of six cancer cell lines revealed that the IC50 values, obtained with cells reported to be sensitive to pro-apoptotic stimuli, are by more than 1 order of magnitude lower than their apoptosis-resistant counterparts (1 vs >80 µM). Finally, three hemisynthetic derivatives of 1 were prepared and evaluated for antiproliferative activity. Two of these possessed IC50 values and differential sensitivity profiles similar to those of 1.

{2-[2,2-Bis(4,4-dimethyl-4,5-di-hydro-1,3-oxazol-2-yl-κN)prop-yl]pyridine}-dichlorido-iron(II).

The title compound,[FeCl2(C18H25N3O2)], has a distorted tetra-hedral Cl2N2 coordination of the Fe(II) atom as a result of the constraints imposed by the 2-[2,2-bis-(4,4-dimethyl-4,5-di-hydro-1,3-oxazol-2-yl)prop-yl]pyridine ligand. The pyridine ring is almost perpendicular to the six-membered chelated ring containing the metal atom [dihedral angle between their mean planes = 88.5 (1)°].