Correction: Identification of the key structural elements of a dihydropyrimidinone core driving toward more potent Hsp90 C-terminal inhibitors.

Correction for 'Identification of the key structural elements of a dihydropyrimidinone core driving toward more potent Hsp90 C-terminal inhibitors' by S. Teracciano et al., Chem. Commun., 2016, 52, 12857-12860.

Identification of the key structural elements of a dihydropyrimidinone core driving toward more potent Hsp90 C-terminal inhibitors.

Hsp90 C-terminal modulation represents an attractive strategy for the development of potent and safer antitumor compounds. Continuing our investigation on DHPM type inhibitors here we report a new set of potent C-terminal ligands which allowed us to identify the key structural features crucial for the biological activity.

ß-Boswellic acid, a bioactive substance used in food supplements, inhibits protein synthesis by targeting the ribosomal machinery.

The Boswellia gum resin extracts have been used in traditional medicines because of their remarkable anti-inflammatory properties. Nowadays, these extracts are on the market as food supplements. ß-Boswellic acid (ßBA) is one of the main pentacyclic triterpene components, among the family of BAs, of the Boswellia gum resins. BAs have been broadly studied and are well known for their wide anti-inflammatory and potential anticancer properties. In this paper, a mass spectrometry-based chemoproteomic approach has been applied to characterize the whole ßBA interacting profile. Among the large numbers of proteins fished out, proteasome, 14-3-3 and some ribosomal proteins were considered the most interesting targets strictly connected to the modulation of the cancer progression. In particular, because of their recent assessment as innovative chemotherapeutic targets, the ribosomal proteins were considered the most attractive ßBA partners, and the biological role of their interaction with the natural compound has been evaluated. Copyright © 2016 John Wiley & Sons, Ltd.

Theonellasterone, a steroidal metabolite isolated from a Theonella sponge, protects peroxiredoxin-1 from oxidative stress reactions.

Peroxiredoxin-1, a key enzyme in the cellular detoxification pathway, has been identified through a chemoproteomic approach as the main partner of theonellasterone, a marine bioactive metabolite. A combination of chemical and biochemical assays disclosed its mechanism of action at the molecular level.

In cell scalaradial interactome profiling using a bio-orthogonal clickable probe.

A bio-orthogonal click-chemistry procedure was developed to allow the in cell interactome profiling of scalaradial, an anti-inflammatory marine natural product. The results were validated through the application of the classical in vitro chemical proteomics and several bio-physical methods; peroxiredoxins, 14-3-3 isoforms and proteasomes were recognized as main scalaradial targets.

Regioselective entry to bromo-gamma-hydroxybutenolides: useful building blocks for assemblying natural product-like libraries.

[reaction: see text] We report a regioselective entry to 3-bromo- and 4-bromo-5-hydroxy-5H-furan-2-ones by photooxidation of 3-bromofuran with a singlet oxygen in the presence of a suitable base. By this procedure, a variety of 3-substituted gamma-hydroxybutenolides have become for the first time easily accessible. Strategies employing these highly functionalized building blocks for the preparation of focused libraries of natural-like molecules are also discussed.

Effect of surface waxes on the persistence of chlorpyrifos-methyl in apples, strawberries and grapefruits.

The effects of the cuticle and epicuticular waxes of grapefruit, strawberry and apple on the photodegradation and penetration of chlorpyrifos-methyl were studied. Photodegradation experiments were conducted by exposing the insecticide to the light of a xenon lamp in the presence of a film of wax extracted from the fruit surface. The half-life of chlorpyrifos-methyl irradiated in absence of waxes was 9.6 min. The half-lives of pesticide irradiated in the presence of wax extracts of apple, grapefruit and strawberry were 83, 34 and 26 min, respectively. In penetration studies, fruit with and without wax layers were treated with an aqueous suspension of pesticide. The penetration of the pesticide from the cuticle to the pulp was measured after 24 h. Samples without wax contained a higher total amount of insecticide than those with wax. No pesticide was detected in samples of apple and grapefruit pulp. Residues were detected in all fractions of strawberry. The waxes and cuticle appear to have some effect on the photodegradation and penetration of chlorpyrifos-methyl in fruit samples.

PLA2-mediated catalytic activation of its inhibitor 25-acetyl-petrosaspongiolide M: serendipitous identification of a new PLA2 suicide inhibitor.

25-Acetyl-petrosaspongiolide M (PMAc) (1), a mild non-covalent PLA(2) inhibitor, unexpectedly recovers, after incubation with bvPLA(2), the ability to covalently modify the enzyme target. This study demonstrates the catalytic effect of bvPLA(2) in converting 1 in its deacetylated congener petrosaspongiolide M (PM) (2), a strong covalent PLA(2) inhibitor whose molecular mechanism of inhibition has already been clarified. Moreover, our findings outline the potential role of PMAc as anti-inflammatory pro-drug, by virtue of its ability of delivering the active PM agent at the site of inflammation, functioning as a suicide inhibitor.

Er:YAG laser treatments on dentine surface: micro-Raman spectroscopy and SEM analysis.

OBJECTIVE: This study aims to give an insight into the chemical and structural modifications occurring in laser treated dentine surface, as a tool to plan a new class of dental materials specific for the dental restoration when laser technologies are used. For this purpose the effect of Er:YAG (Erbium-Yttrium Aluminium Garnet) laser treatments on human dentine surface has been investigated. METHODS: The dentine surface of periodontally compromised teeth cut along the main axis was treated in vitro with laser pulses having the same energy but time duration varying in the range of 100-1000 micros. The chemical characteristics and the morphology of the laser treated surface have been studied with micro-Raman spectroscopy (micro-RS) and scansion electron microscopy (SEM). RESULTS: The micro-RS and SEM analysis of laser treated teeth have been compared with those of surfaces treated with conventional mechanical methodologies. The laser pulse time duration affects the surface morphology and the chemistry of dentine, mainly of organic components. The effects have been monitored by analysing the C-H group stretch vibration mode of the micro-RS spectrum. CONCLUSION: The laser treatment can determine different chemical microenvironments on the treated dentine surface, depending on the time duration of laser pulse used. Treatments with very long pulse results in a the dentine surface very similar to that obtained with a conventional mechanical drill, while with very short laser pulses a strong modification of the dentine organic components has been observed.

Nucleophilic cyclopropane ring opening in duocarmycin SA derivatives by methanol under acid conditions: a quantum mechanical study in the gas-phase and in solution.

We present a quantum-mechanical study of the S(N)2 acid-catalyzed solvolysis with methanol of seven simplified duocarmycin SA (DNA alkylating agent) derivatives characterized by spirocyclic systems of increasing complexity, all containing the cyclopropyl/cyclohexadienone substrate. The reaction has been studied at the DFT-PBE0/6-31G(d) level in the gas phase and in methanol solution, using in the latter case the polarizable continuum model (PCM) to describe solvent effects. The results delivered by this computational protocol are in full agreement with the available experimental evidences and are not modified by extension of the basis set or by using a second-order many-body treatment (MP2) in place of DFT. This allows investigation of substituent effects in terms of structure/reactivity relationships and evaluation of the role of stereoelectronic effects. Furthermore, reactivity indices (hardness, electrophilicity) have been computed and shown to correlate well with activation energies. Together with their intrinsic interest, the details of the mechanism of the acid-catalyzed nucleophilic addition to the activated cyclopropane issuing from the present study pave the route for a deeper understanding of the molecular basis for the remarkable profile of the DNA-alkylation by DSA derivatives.

A new cycloamphilectene metabolite from the Vanuatu sponge Axinella sp.

A new diterpene, N-formyl-7-amino-11-cycloamphilectene (1), was isolated from the apolar extract of the Vanuatu sponge Axinella sp. The structure and relative stereochemistry were established by spectroscopic and single-crystal X-ray studies.

Makaluvamine P, a new cytotoxic pyrroloiminoquinone from Zyzzya cf. fuliginosa.

A new pyrroloiminoquinone alkaloid (1) belonging to the makaluvamine family has been isolated from the sponge Zyzzya cf. fuliginosa collected in the waters off the Vanuatu Islands. The compound, designated makulavamine P, was characterized on the basis of its spectral data and displayed cytoxicity in the microM range on KB cells and antioxidant activity.

Isolation and NMR characterization of rosacelose, a novel sulfated polysaccharide from the sponge Mixylla rosacea.

Rosacelose, a new anti-HIV polysaccharide composed of glucose and fucose sulfate, has been isolated from an aqueous extract of the marine sponge Mixylla rosacea. Extensive use of 1H and 13C multidimensional NMR spectroscopy, combined with chemical analysis were used to establish a linear polysaccharide structure composed mainly of 4,6-disulfated 3-O-glycosylated alpha-D-glucopyranosyl and 2,4-disulfated 3-O-glycosylated alpha-L-fucopyranosyl residues (in a 3:1 molar ratio).

New bisindole alkaloids of the topsentin and hamacanthin classes from the Mediterranean marine sponge Rhaphisia lacazei.

Chemical investigation of the Et(2)O extract of the marine sponge Rhaphisia lacazei resulted in the isolation of 13 pure bisindole alkaloids (1-13). Compounds (1-6) belong to the class of topsentins and have already been described. Compounds 7-13 are new products, closely related to the class of hamacanthins. The major compounds 1-3 were tested in vitro for antitumor activity; compounds 2 and 3 showed antiproliferative activity against human bronchopulmonary cancer cells (NSCLC-N6) with an IC(50) of 12 and 6.3 microg/mL, respectively.

Steroid and triterpenoid oligoglycosides of marine origin.

Saponins have been considered for a long time typical metabolites of plant origin. It has been only in the last two decades that the world-wide investigation of marine organisms as sources of new bioactive metabolites disclosed the wide distribution of these molecules also among marine animals. Today saponins are recognized as the most common characteristic metabolites in two classes of the phylum Echinodermata (Holothuroidea and Asteroidea). Furthermore, several steroid and triterpenoid oligoglycosides have been isolated from different species of marine sponges, more rarely Anthozoans, and also from fishes of the genus Pardachirus, where they have been shown to act as shark repellents. This communication offers a general view of the distribution of steroid and triterpenoid oligoglycosides among marine organisms and focuses on a number of recent examples to discuss structural characteristics, biological activities, and methods of investigation.

Further brominated bis- and tris-indole alkaloids from the deep-water New Caledonian marine sponge Orina Sp.

Two tris-indole alkaloids, (+/-) gelliusines A and B [1], have been isolated for the first time from a marine source, the New Caledonian sponge, Orina sp. (or Gellius sp.), along with five further indole constituents [2-6]. Compound 6 has been identified as 2,2-bis-(6'-bromo-3'-indolyl(-ethylamine, previously isolated from the tunicate Didemnum candidum, but the remaining four indoles [2-5] are novel compounds. These showed anti-serotonin activity and a strong affinity for somatostatin and neuropeptide Y receptors in receptor-binding assays.