Diselenide Covalent Allosteric Inhibitors of Glutaminase with Strong Anticancer Activity.

Allosteric glutaminase inhibitors demonstrate inhibition of glutamine-dependent cancer cells with low general drug toxicity, but have issues with efficacy . Here, we designed a series of diselenide compounds with 6 atoms in the middle, aiming to target the allosteric site of kidney type glutaminase (KGA) with a covalent linkage to strengthen the interaction. Proteomic analysis demonstrated that the diselenide compounds cross-linked with the Lys320 residue at the KGA allosteric site; this was confirmed by the KGA K320A mutant which showed essentially no binding to the diselenide.

Design and synthesis of novel tellurodibenzoic acid compounds as kidney-type glutaminase (KGA) inhibitors.

Organotellurium compounds have been reported as an immune-modulator sensitizing chemotherapeutics. Herein, we report the design and synthesis of a series of novel tellurodibenzoic acids as mimics of diphenylarsenic acid (DPAA) and potential selective KGA inhibitors. Representative compound 3B exhibited potent inhibition of KGA and glutamine-dependent HCT-116 cells.

Chemosensors for biogenic amines and biothiols.

There is burgeoning interest among supramolecular chemists to develop novel molecular systems to detect biogenic amines and bio-thiols in aqueous and non-aqueous media due to their potential role in biological processes. Biogenic amines are biologically important targets because of their involvement in the energy metabolism of human biological systems and their requirement is met through food and nutrition. However, the increasing instances of serious health problems due to food toxicity have raised the quality of food nowadays.

Facile synthesis, structural evaluation, antimicrobial activity and synergistic effects of novel imidazo[1,2-a]pyridine based organoselenium compounds.

A simple and efficient method has been described to synthesize the hitherto unknown imidazo[1,2-a]pyridine selenides (5a-l) by reaction of 2-chloroimidazo [1,2-a]pyridines with aryl/heteroaryl selenols, generated in situ by reduction of various diselenides with hypophosphorous acid. The crystal structures of 3-nitro-2-(phenylselanyl)-imidazo[1,2-a]pyridine (5a), 2-(mesitylselanyl)-3-nitro-imidazo[1,2-a]pyridine (5d) and 3-nitro-2-(pyridin-2-ylselanyl)-imidazo[1,2-a]pyridine (5e) were confirmed by X-ray crystallography and the DFT calculations were performed to determine various structural parameters which were correlated with the X-ray crystal structures. The synthesized compounds were subjected to antimicrobial evaluation and it was found that compounds 5a and 5j were active against gram negative bacterium Escherichia coli whereas compound 5e was active against different fungal strains.

Synthesis of the AB ring system of clifednamide utilizing Claisen rearrangement and Diels-Alder reaction as key steps.

In order to construct the functionalized AB ring system of clifednamide, member of the class of macrocyclic tetramic acid lactams, a synthesis was developed which utilized an Ireland-Claisen rearrangement and an intramolecular Diels-Alder reaction. Starting from di-O-isopropylidene-d-mannitol the allyl carboxylate precursor for the sigmatropic rearrangement was prepared. This rearrangement proceeded diastereoselectively only in the presence of an allyl silyl ether instead of the parent enone in the side chain, as suggested by deuteration experiments.

Plasmon enhanced fluoro-immunoassay using egg yolk antibodies for ultra-sensitive detection of herbicide diuron.

Plasmon enhanced fluorescence immunoassay (PEFI) format has been reported in developing a sensitive heterogeneous fluoroimmunoassay for monitoring the phenylurea herbicide diuron. Computer-assisted molecular modeling was carried out to study the conformational and electrostatic effects of synthesized hapten for producing highly specific egg yolk antibody against a phenyl urea herbicide diuron. The generated antibodies were labeled with fluorescein isothiocyanate at different molar ratios and used as tracer in the developed fluorescence based immunoassay.

Gold nanoparticles catalyzed chemiluminescence immunoassay for detection of herbicide 2,4-dichlorophenoxyacetic acid.

We present a novel immunoassay format utilizing the catalytic properties of gold nanoparticles in the luminol-silver nitrate-gold nanoparticle based chemiluminescence (CL) system for the detection of widely used herbicide 2,4-dichlorophenoxyacetic acid (2,4-D). Highly sensitive anti-2,4-D antibody was produced and conjugated with gold nanoparticles of various sizes. In the present assay format, employing a competitive inhibition approach, a well-characterized hapten-protein conjugate (2,4-D-BSA) was used to coat the microtiter plates.