Discovery of T-1101 tosylate as a first-in-class clinical candidate for Hec1/Nek2 inhibition in cancer therapy.

Highly expressed in cancer 1 (Hec1) plays an essential role in mitosis and is correlated with cancer formation, progression, and survival. Phosphorylation of Hec1 by Nek2 kinase is essential for its mitotic function, thus any disruption of Hec1/Nek2 protein-protein interaction has potential for cancer therapy. We have developed T-1101 tosylate (9j tosylate, 9j formerly known as TAI-95), optimized from 4-aryl-N-pyridinylcarbonyl-2-aminothiazole of scaffold 9 by introducing various C-4' substituents to enhance potency and water solubility, as a first-in-class oral clinical candidate for Hec1 inhibition with potential for cancer therapy.

Synthesis and structure-activity relationship of 3-O-acylated (-)-epigallocatechins as 5α-reductase inhibitors.

A series of 3-O-acylated (-)-epigallocatechins were synthesized and their inhibition of steroid 5α-reductase was studied. They were prepared from the reaction of EGCG with tert-butyldimethylsilyl chloride followed by reductive cleavage of the ester bond. The resultant (-)-epigallocatechins penta-O-tert-butyldimethylsilyl ether was esterified with different fatty acids then desilylated to provide the corresponding products.

Bioconjugation of 32-macrocyclic polyammonium cations-functionalized gold nanoparticles with BSA.

Water-dispersed, spherical, underivatized Au-NPs with particle size less than 5 nm were synthesized from an aqueous solution of 32-macrocyclic polyammonium chloride, [32]ane-(NH(2)(+))(8).8Cl(-) (32-MCPAC) using sodium borohydride (NaBH(4)) as the reducing agent. The bioconjugation of the synthesized Au-NPs at different pHs (3.

Functionalized carbon nanotubes as the pseudostationary phase for capillary EKC separation of non-steroidal anti-inflammatory drugs.

Functionalized multiwalled carbon nanotubes (f-MWCNTs) can serve as the pseudostationary phase (PSP) for the capillary EKC separation of non-steroidal anti-inflammatory drugs (NSAIDs). To increase their hydrophilicity, we treated MWCNTs, with a sonochemical process in a concentrated nitric/sulfuric acid mixture. The oxidized MWCNTs were then characterized by FT-IR, transmission electron microscopy, and X-ray photoelectron spectroscopy.

Preparation and characterization of monoliths covalently bonded chelating groups for capillary electrochromatographic separation of metal ions.

In this work, a novel polymer-based monolithic column was prepared using an o-phthalaldehyde-l-phenylalanine Schiff base complex as the reactive center and a mixture of methanol and n-propanol as the porogen. The monolithic column was employed for the separation of a metal ion mixture including Pb(II), Mn(II), Cu(II), Ni(II), Cr(III), Fe(III) and Cr(VI). Tetrabutylammonium bromide (TBAB) was used as a mobile phase additive to enhance the separation efficiency of metal ions by EDTA precomplexation.

Preparation and application of ionic liquid-coated fused-silica capillary fibers for solid-phase microextraction.

A simple and cost effective solid-phase microextraction device has been developed. Fused-silica capillaries were etched with ammonium hydrogen difluoride prior to coating with an ionic liquid. For comparison, both a bare fused-silica capillary and one pretreated with a Nafion membrane were coated with the ionic liquid.

Novel stationary phase for complexation gas chromatography originating from ionic liquid and metallomesogen.

A metallomesogen of a polycatenar oxazoline copper(II) complex, [Cu(S-C(12))(2)], that exhibited a columnar mesophase with a helical organization was prepared and employed as the stationary phase for the GC separation with polycyclic aromatic hydrocarbons (PAHs) as model compounds. For introducing the mesogen into the capillary column, an ionic liquid (BeMIM-TfO) was used as the vehicle. The results of thermal analyses and UV-vis spectroscopy indicated that some beneficial interactions occurred between the metallomesogen and the ionic liquid.

Separation of corticosteroids by microemulsion EKC with diethyl L-tartrate as the oil phase.

A novel microemulsion based on a mixture of diethyl L-tartrate (DET) and SDS was developed for the microemulsion EKC (MEEKC) determination of structurally related steroids. The system consisted of 0.5% w/w DET, 1.