A 14-residue peptide toxin has been isolated from the venom of the marine snail Conus magus. Its amino acid sequence, GlyArgCysCysHisProAlaCysGly LysAsnTyrSerCysNH2, is homologous with those of the previously described conotoxins GI, GII, and GIA from Conus geographus...

Milked venoms of Conus demonstrate direct lineage to US Food and Drug Administration approved and present in-trial drug leads. Yet the complexity of the milked venom has not been adequately investigated or characterized, in a sustainable manner. In this study we determine the extent of molecular...

A concise and efficient synthesis of novel bicyclic pyrroles has been achieved by PdCl2-catalyzed cyclic condensation of six-membered heterocyclic ketene aminals (HKAs) or seven-membered HKAs with ethyl 2,3-diiodoacrylate and diethyl 2,3-diiodofumarate in the presence of Cs2CO3, respectively. A ...

New pyrrolo[1,2-c]pyrimidines derivates having a biphenyl moiety at position 3 have been synthesized by 1,3-dipolar cycloaddition of their corresponding N-ylides with activated alkynes. FTIR, 1H and 13C NMR spectroscopy and elemental analysis have been used to characterize the structures of the ...

An efficient approach for the synthesis of 3,5-dihydro-4H-pyrimido[5,4-b]indol-4-one derivatives has been developed. The key compound isothiocyanate was prepared through a simple and ecological method using di-2-pyridyl thionocarbonate (DPT) in substitution of the thiophosgene, a potential air p...

Trichosporin (TS) -B-VIa, a fungal α-aminoisobutyric acid (Aib) -containing peptide consisting of 19 amino acid residues and a phenylalaninol, produced both 45Ca2+ influx into bovine adrenal chromaffin cells and catecholamine secretion from the cells. The secretion induced by TS-B-VIa at lower ...

The NMDA receptor containing GluN2B subunits represents a promising target for the development of drugs for the treatment of various neurological disorders including neurodegenerative diseases. In order to study the role of CH3 and OH moieties trisubstituted tetrahydro-3-benzazepines 4 were desi...

The role of the phenolic and benzylic OH moieties for the interaction of tetrahydro-3-benzazepine-1,7-diol 3d with GluN2B subunit containing NMDA receptors was analyzed by their stepwise removal. Elimination of trifluormethanesulfinate from 10 and 13 represent the key steps in the synthesis. Rem...

The class of tetrahydro-1H-3-benzazepines was systematically modified in 1-, 3- and 7-position. In particular, a F-atom was introduced in β- or γ-position of the 4-phenylbutyl side chain in 3-position. Ligands with the F-atom in γ-position possess higher GluN2B affinity than analogs bearing t...

Garcinia mangostana L. (Mangosteen) has been used to treat various pathological conditions, including inflammation and urinary tract infections. Here, we observed that garcinone D, a natural xanthone from mangosteen, promoted the proliferation of C17.2 neural progenitor cells and also resulted i...

A series of novel benzamide derivatives, altering the 4-fluorophenylalkyl moiety in cisapride, were synthesized as 5-HT4 receptor agonists, and SAR of these analogs was examined on in vitro and in vivo prokinetic activities. These compounds were synthesized for high 5-HT4 receptor binding affini...

Through virtual screening, we identified the lead compound MCL1020, which exhibited modest CHK1 inhibitory activity. Then a series of 5-(pyrimidin-2-ylamino)picolinonitrile derivatives as CHK1 inhibitors were discovered by further rational optimization. One promising molecule, (R)-17, whose pote...

A one-pot domino reaction involving Lewis acid-mediated nucleophilic-substitution/intramolecular-cyclization/reverse Claisen condensation of 2-(aryl(piperidin-1-yl)methyl)phenols and 1,3-diketones has been developed for the synthesis of 2-(3-oxo-1-phenylbutyl)phenyl acetates in good to excellent...

5-Oxo-4,5,6,7-tetrahydro-1H-pyrrolo[3,2-b]pyridine-3-carboxylic acids were prepared by three-component condensation of 3-aminopyrroles, (het)aromatic aldehydes and Meldrum's acid. The labile intermediate 3-aminopyrrole derivative was generated in situ by regioselective (at 2-position) decar...

Protein arginine methyltransferases 5 (PRMT5) represents an attractive drug target in epigenetic field for the treatment of leukemia and lymphoma. Here, a series of N-(3-(3,4-dihydroisoquinolin-2(1H)-yl)-2-hydroxypropyl)amide derivatives targeting PRMT5 were designed with structure-based approac...

Liposomes prepared from DMPC (80%) and cholesterol (20%) were modified with a series of hydrophobically modified N-substituted polyacrylamides, namely, poly[N-isopropylacrylamide] (PNIPAM), poly[N,N-bis(2-methoxyethyl) acrylamide] (PMEAM), and poly[(3-methoxypropyl)acrylamide] (PMPAM). The hydro...

ObjectivesThis study aimed to develop silver nanoparticle (AgNP)-doped Ti6Al4V alloy surfaces and investigate their antibacterial properties against representative periopathogens and potential cytotoxicity on osteoblastic cells.

Palladium-based alloys have had a significant import on the fabrication of ceramometal restorations. This article compares the bond strengths of four palladium-based alloys with that of a high-noble alloy. Tests were designed to closely represent clinical situations. Bond strengths of the pallad...

Strength of a soldered palladium alloy, PGC (Engelhard Corp.), and a soldered medium gold alloy, PGX (Engelhard Corp.), was examined. The results obtained were as follows:1. Highest strength was observed with postsoldered specimens of PGC alloy.2. Microstructural examination of postsoldered spec...

A 2 kb DNA region of the broad-host-range plasmid pCU1 carries all of the information essential for the stable maintenance of the plasmid and to express the same host-range specificity. It was predicted that the protein required to initiate replication from at least one of the three origins of t...