Visual detection of cysteine and homocysteine

The determination of cysteine and homocysteine levels is of great current interest for the monitoring of desease states. A new colorimetric method for the simultaneous detection of l-cysteine and l-homocysteine has been developed. A fluorescein derivative reacts with the above amino acids, producing their respective thiazolidines resulting in color changes. Interference from other amino acids and proteins is minimal.     

Synthesis of <Emphasis Type="Italic">O</Emphasis>-[2-[<Superscript>18</Superscript>F]fluoro-3-(2-nitro-1<Emphasis Type="Italic">H</Emphasis>-imidazole-1-yl)propyl]tyrosine ([<Superscript>18</Superscript>F]FNT]) as a new class of tracer for imaging hypoxia

For detection of hypoxic tumor tissue, all radiotracers synthesized until now, are based on the concept that cellular uptake is being controlled by diffusion. As a new approach, we chose the concept to have the tracer hypothetically transported into the cells by well known carrier systems like the amino acid transporters. For this purpose, radiosynthesis of O-[2-[¹⁸F]fluoro-3-(2-nitro-1H-imidazole-1yl)propyl]tyrosine ([¹⁸F]FNT]) was carried out from methyl 2-(benzyloxycarbonyl)-3-(4-3-(2-nitro-1H-imidazol-1-yl)-2-(tosyloxy)propoxy) phenyl)propanoate via no-carrier-added nucleophilic aliphatic substitution. After labelling, 81 ± 0.9% of labelled intermediate i.e. methyl 2-(benzyloxycarbonyl)-3-(4-(2-[¹⁸F]fluoro-3-(2-nitro-1H-imidazole-1-yl)propoxy) phenyl)propanoate was obtained at 140 °C. At the end of radiosynthesis, [¹⁸F]FNT was obtained in an overall radiochemical yield of 40 ± 0.9% (not decay corrected) within 90 min in a radiochemical purity of >98% in a formulation ready for application in the clinical studies for PET imaging of hypoxia.     

Anti-angiogenic activity of Morinda citrifolia extracts and its chemical constituents

Morinda citrifolia L. has been used for the treatment of a wide variety of diseases, including cancer. This study was undertaken to evaluate the anti-angiogenic effect of M. citrifolia fruits and leaves. Anti-angiogenic activity was evaluated in?vivo using the chick chorioallantoic membrane assay. Bioactivity-guided fractionation and isolation were performed to identify the active constituent, and high-performance liquid chromatography analysis was then used to quantify the amount of this active constituent in the active extracts and fraction. The methanol extracts of fruits and leaves of M. citrifolia and the subsequent chloroform fraction of the fruit methanolic extract were found to have potential anti-angiogenic activity and were more potent compared to suramin. Scopoletin was identified as one of the chemical constituents that may be partly responsible for the anti-angiogenic activity of M. citrifolia fruits. The present findings further support the use of M. citrifolia in cancer or other pathological conditions related to angiogenesis.     

Phytochemical analysis, cytotoxic activity and constituents-activity relationships of the leaves of Cinnamomum iners (Reinw. ex Blume-Lauraceae)

The leaves of Cinnamomum iners (Reinw. ex Blume-Lauraceae) have been refluxed successively with chloroform and alcohol to get chloroform extract and alcoholic extract. Both the extracts have been assayed for cytotoxicity against human colorectal tumour cells. The chloroform extract exhibited significant cytotoxicity with IC(50) 31?μg mL(-1) (p??200?μg mL(-1). The chloroform extract has been further proceeded for chemical analysis by GC-TOFMS and 178 components were identified including acids, amines, amides, aldehydes, alcohols, esters, benzene derivatives, bicyclic compounds, terpenes, hydrocarbons, naphthalene derivatives, furan derivatives, azulenes, etc. Nine components representing 51.73% of the total chloroform extract were detected as major components. Caryophyllene (14.41%) and Eicosanoic acid ethyl ester (12.17%) are the most prominent components of the chloroform extract. β-Caryophyllene (14.41%) as most abundant compound supports potent cytotoxicity as shown by chloroform extract.     

Sulfonimidamides and Imidosulfuric Diamides: Compounds from an Underexplored Part of Biologically Relevant Chemical Space

Two novel solid reagents—1-sulfonimidoyl- and 1-sulfamimidoyl-3-methylimidazolium derivatives—for the synthesis of sulfonimidamides and imidosulfuric diamides, respectively, were developed. It is shown that these reagents are very effective in substitution reactions with various N- and O-nucleophiles; therefore, they significantly extend the accessibility to the chemical space covered by organosulfur(VI) compounds with S=N bonds. In addition, previously unknown imidosulfuric diamides with free imino nitrogen groups were prepared, and their physical and chemical properties were characterized (including molecular geometry, pK_a, Log P, microsomal stability, and reactivity towards typical electrophiles). Similar to other organosulfur(VI) derivatives with S=N bonds, these compounds can be considered as promising bioisosteres of amides, ureas, or sulfonamides.     

FLUORESCENCE SPECTRAL CHANGES OF HEMATOPORPHYRIN DERIVATIVE UPON BINDING TO LIPID VESICLES, Staphylococcus aureus AND Escherichia coli CELLS

Abstract— The binding of hematoporphyrin derivated (Hpd) to lipid vesicles and bacterial membranes was determined by fluorescence spectroscopy. The fluorescence measurements of Hpd in aqueous solutions showed two bands at 613 and 677 nm. In lipid environments of lecithin vesicles the fluorescence spectrum was shifted to 631 and 692 nm, respectively. Hpd was rapidly bound to the cell membrane of Staphylococcus aureus while much less binding occurred in the presence of Escherichia coli. At the same time, spheroplasts of both bacteria were shown to bind Hpd to a similar extent. These results are well correlated with the photoinactivation of the gram positive bacteria with Hpd while the gram negative cells were shown to be resistant. The pH dependence of both Hpd binding to S. aureus as well as the photodynamic inhibitory effect of the same bacteria are similar. It is concluded that the segregation of Hpd to the cell membrane is a prerequisite for its photodynamic effect.     

A novel single source precursor: [bis(N,N-diethyl-N'-naphthoyl-selenoureato)palladium(II)] for palladium selenide thin films and nanoparticles

We describe for the first time the use of a single source precursor to deposit thin films and nanocrystals of palladium selenide.     

Modified AutoDock for accurate docking of protein kinase inhibitors

Protein kinases are an important class of enzymes controlling virtually all cellular signaling pathways. Consequently, selective inhibitors of protein kinases have attracted significant interest as potential new drugs for many diseases. Computational methods, including molecular docking, have increasingly been used in the inhibitor design process [1]. We have considered several docking packages in order to strengthen our kinase inhibitor work with computational capabilities. In our experience, AutoDock offered a reasonable combination of accuracy and speed, as opposed to methods that specialize either in fast database searches or detailed and computationally intensive calculations.However, AutoDock did not perform well in cases where extensive hydrophobic contacts were involved, such as docking of SB203580 to its target protein kinase p38. Another shortcoming was a hydrogen bonding energy function, which underestimated the attraction component and, thus, did not allow for sufficiently accurate modeling of the key hydrogen bonds in the kinase-inhibitor complexes.We have modified the parameter set used to model hydrogen bonds, which increased the accuracy of AutoDock and appeared to be generally applicable to many kinase-inhibitor pairs without customization. Binding to largely hydrophobic sites, such as the active site of p38, was significantly improved by introducing a correction factor selectively affecting only carbon and hydrogen energy grids, thus, providing an effective, although approximate, treatment of solvation.     

Micellization and Clouding Phenomenon of Phenothiazine Drug Promethazine Hydrochloride: Effect of NaCl and Urea Addition

Herein we report the micellization and clouding behavior of promethazine hydrochloride (PMT) in absence and presence of NaCl/ureas. The critical micelle concentration (CMC) of PMT is measured by conductivity method and the values decrease with increasing the NaCl concentration. With increasing the temperature, the CMC first increases then decreases. At 25°C, the maximum CMC values were obtained (with or without NaCl). The thermodynamic parameters are evaluated which indicate more stability of the PMT solution in presence of NaCl. PMT shows phase separation also. The cloud point (CP) of PMT decreases with increase in pH due to deprotonation of the drug molecules. Ureas decreased the CP and the behavior is explained on the basis of removal of water from the head group region.     

Tyrosinase-inhibitory long-chain esters from Amberboa ramosa

Long-chain esters 1 and 2 have been isolated from the chloroform-soluble fraction of Amberboa ramosa and their structures assigned to be methyl 2beta(2S)-hydroxyl-7(E)-tritriacontenoate (1) and methyl 2beta(2S)-O-beta-D-galactopyranosyl-7(E)-tetratriacontenoate (2). In addition, tricontane (3) and apigenin (4) are also reported for the first time from this species. The structures were assigned on the basis of 1D and 2D NMR techniques. Compounds 1 and 2 showed strong to moderate inhibitory activity against tyrosinase.