Novel small-molecule inhibitors of arylamine N-acetyltransferases: drug discovery by high-throughput screening

Arylamine N-acetyltransferases (NATs) are a family of enzymes found in eukaryotes and prokaryotes. While the precise endogenous function of NAT remains unknown for most organisms, recent evidence has shown that the expression of human NAT1 is up-regulated in estrogen receptor positive breast cancer. Additionally, NAT in mycobacteria is required for mycobacterial cell wall biosynthesis and survival of the organisms within macrophage. It is therefore important to develop small molecule inhibitors of NATs as molecular tools to study the function of NATs in various organisms. Such inhibitors may also prove useful in future drug design, for example in the development of anti tubercular agents. We describe a high-throughput screen of a proprietary library of 5016 drug-like compounds against three prokaryotic NAT enzymes and two eukaryotic NAT enzymes.     

UV protection and singlet oxygen quenching activity of aloesaponarin I

The UV protection and singlet oxygen quenching of aloesaponarin I have been studied by means of laser spectroscopy. The excited-state intramolecular proton transfer that provides the UV protection takes place along only one of the molecule's two intramolecular hydrogen bonds, and this can be understood by considering the nodal pattern of the wave function. The functional groups participating in the excited-state intramolecular proton transfer also play important roles in the singlet oxygen quenching. Aloesaponarin I has a quenching rate constant larger than that of vitamin E and has a long duration of action due to its resistance to UV degradation and chemical attacks by singlet oxygen and free radicals.     

Efficient refractive-index modification of fused silica by a resonance-photoionization-like process using F(2) and KrF excimer lasers

Novel materials processing by a multiwavelength excitation process using F(2) and KrF excimer lasers for high-efficiency and high-speed refractive-index modification of fused silica is demonstrated. We find this process to be essentially superior to single-wavelength F(2) -laser processing: The multiwavelength excitation process achieves more than twice the diffraction efficiency of fused silica modified by a F(2) laser at the same total number of photons in each irradiated laser beam supplied to the fused-silica substrate. This superiority is attributed to a resonance-photoionization-like process based on excited-state absorption.     

Synthesis and properties of polyimide–clay hybrid

A polyimide hybrid with montmorillonite clay mineral has been synthesized from a dimethylacetamide (DMAC) solution of poly(amic acid) and a DMAC dispersion of montmorillonite intercalated with an ammonium salt of dodecylamine. Montmorillonite consists of stacked silicate sheets about 2000 Å in length, 10 Å in thickness. In this hybrid, montmorillonite is dispersed homogeneously into the polyimide matrix and oriented parallel to the film surface. Thanks to this special structure, this hybrid showed excellent gas barrier properties. Only 2 wt % addition of montmorillonite brought permeability coefficients of various gases to values less than half of those of ordinary polyimide. Furthermore, this hybrid had low thermal expansion coefficient. © 1993 John Wiley & Sons, Inc.     

Novel memory effect found in nematic liquid crystal/fine particle system

Novel liquid crystalline composites composed of a nematic two-frequency-addressing liquid crystal and organized clay mineral (about 1 wt %) have been prepared. The particles of clay mineral were dispersed homogeneously in the liquid crystal. The composite cells became transparent within 50ms when a 60 Hz electric field was applied. The transparent state was maintained after the field was switched off. It transformed into a turbid light scattering state by applying 1.5 kHz electric field which caused dynamic scattering in the cell. The light transmittance of both memory states did not change after 20 h without the electric field.     

Syntheses and properties of tetraaza‐, diaza‐, tetraoxa‐, and dioxa‐metacyclophanes

Metacyclophanes were prepared by cyclization reactions between bis(chloromethyl) compounds and piperazine, primary amines, or ethylene glycol. The ¹H nmr relaxation time (T₁) measurements indicated that the macrocycles feature the up and down motion of the aromatic units around the XCH₂Ar (X = N, O) methylene moieties as the axes. Metacyclophanes incorporating piperazine units showed high complexation ability for alkaline metal cations.     

Synthesis of N,N′-bridged azacalixarenes

The one-pot reaction between bis(hydroxymethyl)phenol derivatives and diamines or triamines afforded novel azacalixarenes with bridged structures. Basket-type macrocycles of cone conformations, molecules that contained two aza[3.1.1.1]calixarene skeletons connected by a chain, or novel saucer-type azacalixarenes were obtained from the reaction. Structures of some of them were determined by crystallographic analyses.