Novel N-(4-Piperidinyl)benzamide antimalarials with mammalian protein farnesyltransferase inhibitory activity

Protein farnesyltransferase of Plasmodium falciparum is a potential target in the treatment of malaria for which increased drug resistance is observed. The design, synthesis and evaluation of a series of N-(4-piperidinyl)benzamides is reported. The most potent compounds showed in vitro activity against the parasite at submicromolar concentrations.     

Foreword

Journal of Radioanalytical and Nuclear Chemistry -     

Chebyshev splines and shape parameters

A parametric spline curve is defined whose restriction to each sub-interval belongs to a 4-dimensional piecewise Chebyshev subspace depending on coefficients which play the role of shape parameters. This revised version was published online in August 2006 with corrections to the Cover Date.     

Synthesis, spectral characterization, and thermal behavior of mononuclear Cu(II), Co(II), Ni(II), Mn(II), and Zn(II) complexes with 5-bromosalycilaldehyde isonicotinoylhydrazone

A bidentate/tridentate 5-bromosalycilaldehyde isonicotinoylhydrazone Schiff base was synthesized by condensing 5-bromosalycilaldehyde with isonicotinoylhydrazine. Cu(II), Co(II), Ni(II), Mn(II) and Zn(II) complexes of this chelating ligand were synthesized using nitrates of these metals. The ligand and the complexes were characterized by elemental analysis, UV–Vis, IR and EPR spectroscopy, conductance and magnetic susceptibility measurements, fluorescence, cyclic voltammetry and thermogravimetric analysis. The ligand and Zn(II) complex exhibits solid-state photoluminescence at room temperature.     

Nonequilibrium phases of nanoparticle Langmuir films

We report on an in-situ observation of the colloidal silver nanoparticle self-assembly into a close-packed monolayer at the air/water interface followed by a 2D to 3D transition. Using the fast tracking GISAXS technique, we were able to observe the immediate response to the compression of the self-assembled nanoparticle layer at the air/water interface and to identify all relevant intermediate stages including those far from the equilibrium. In particular, a new nonequilibrium phase before the monolayer collapse via the 2D to 3D transition was found that is inaccessible by the competing direct space imaging techniques such as the scanning and transmission electron microscopies due to the high water vapor pressure and surface tension.     

Hypervalent Organoselenium(II) Compounds with Organophosphorus Ligands. Crystal and Molecular Structure of [2‐(iPr2NCH2)C6H4]Se[S2PR′2] (R′ = Ph,OiPr)

Redistribution reactions between diorganodiselenides of type [2‐(R₂NCH₂)C₆H₄]₂Se₂ [R = Et, iPr] and bis(diorganophosphinothioyl disulfanes of type [R′₂P(S)S]₂ (R = Ph, OiPr) resulted in the hypervalent [2‐(R₂NCH₂)C₆H₄]SeSP(S)R′₂ [R = Et, R′ = Ph ( 1 ), OiPr ( 2 ); R = iPr, R′ = Ph ( 3 ), OiPr ( 4 )] species. All new compounds were characterized by solution multinuclear NMR spectroscopy (¹H, ¹³C, ³¹P, ⁷⁷Se) and the solid compounds 1 , 3 , and 4 also by FT‐IR spectroscopy. The crystal and molecular structures of 3 and 4 were determined by single‐crystal X‐ray diffraction. In both compounds the N(1) atom is intramolecularly coordinated to the selenium atom, resulting in T‐shaped coordination arrangements of type (C,N)SeS. The dithio organophosphorus ligands act monodentate in both complexes, which can be described as essentially monomeric species. Weak intermolecular S ··· H contacts could be considered in the crystal of 3 , thus resulting in polymeric zig‐zag chains of R and S isomers, respectively.     

Electrochemical oxidation of p-nitrophenol using graphene-modified electrodes, and a comparison to the performance of MWNT-based electrodes

The electrochemical oxidation of p-nitrophenol (p-NP) has been studied comparatively on a graphene modified electrode and a multiwall carbon nanotube (MWNT) electrode by using cyclic and differential pulse voltammetry. The sensors were fabricated by modifying screen-printed electrodes with graphene and MWNT nanomaterials, respectively, both dispersed in Nafion polymer. p-NP is irreversibly oxidized at +0.9?V (vs. the Ag/AgCl) in solutions of pH 7. The height and potential of the peaks depend on pH in the range from 5 to 11. In acidic media, p-NP yields a well-defined oxidation peak at +0.96?V which gradually increases in height with the concentration of the analyte. In case of differential pulse voltammetry in sulfuric acid solution, the sensitivity is practically the same for both electrodes. The modified electrodes display an unusually wide linear response (from 10???M to 0.62?mM of p-NP), with a detection limit of 0.6???M in case of the graphene electrode, and of 1.3???M in case of the MWNT electrode.

Formation of Integral Asymmetric Membranes of AB Diblock and ABC Triblock Copolymers by Phase Inversion

The formation of integral asymmetric membranes from ABC triblock terpolymers by non‐solvent‐induced phase separation is shown. They are compared with the AB diblock copolymer precursors. Triblock terpolymers of polystyrene‐block‐poly(2‐vinylpyridine)‐block‐poly(ethylene oxide) (PS‐b‐P2VP‐b‐PEO) with two compositions are investigated. The third block supports the formation of a membrane in a case, where the corresponding diblock copolymer does not form a good membrane. In addition, the hydrophilicity is increased by the third block and due to the hydroxyl group the possibility of post‐functionalization is given. The morphologies are imaged by scanning electron microscopy. The influence of the PEO on the membrane properties is analyzed by water flux, retention, and dynamic contact angle measurements.

     

Conjugates of Cryptophycin and RGD or isoDGR Peptidomimetics for Targeted Drug Delivery

RGD-cryptophycin and isoDGR-cryptophycin conjugates were synthetized by combining peptidomimetic integrin ligands and cryptophycin, a highly potent tubulin-binding antimitotic agent across lysosomally cleavable Val-Ala or uncleavable linkers. The conjugates were able to effectively inhibit binding of biotinylated vitronectin to integrin α_vβ₃, showing a binding affinity in the same range as that of the free ligands. The antiproliferative activity of the novel conjugates was evaluated on human melanoma cells M21 and M21-L with different expression levels of integrin α_vβ₃, showing nanomolar potency of all four compounds against both cell lines. Conjugates containing uncleavable linker show reduced activity compared to the corresponding cleavable conjugates, indicating efficient intracellular drug release in the case of cryptophycin-based SMDCs. However, no significant correlation between the in vitro biological activity of the conjugates and the integrin α_vβ₃ expression level was observed, which is presumably due to a non-integrin-mediated uptake. This reveals the complexity of effective and selective α_vβ₃ integrin-mediated drug delivery.     

Nanostructured Au/Si substrate for organic molecule SERS detection

Nanoparticles of noble metals, such as gold and silver, exhibit unique and tunable optical properties on account of their surface plasmon resonance. In particular, gold nanoparticles on silicon substrates are attractive for future nanoscale sensors and optical devices due to their resistance to oxidation and due to their electrical and optical properties. In this study, we developed a nanostructured gold/macroporous silicon (Au/PS) substrate capped with 11-mercaptoundecanoic acid (11-MUA) with ultra-sensitive detection properties achieved in characterization, an approach based on surface-enhanced Raman scattering (SERS). Surface-enhanced Raman scattering allows us to detect substances at a low concentration level and to observe structural details of a thiol molecule bonded to small film thicknesses. Raman measurements were carried out at 514 nm and 785 nm. In order to emphasize the effect of the Si microstructuration on the efficiency of this new substrate (Au/PS) proposed for SERS experiments, the same molecule (11-MUA) was adsorbed on it as well as on gold/atomically flat silicon (Au/Si) and on commercial Klarite (Mesophotonics) substrates. Systematic studies realized by Raman spectroscopy, electron microscopy, and X-ray spectroscopy show the influence of silicon substrate texturing and metallic deposition conditions, including time and temperature on the optical phenomena.