Single Tryptophan of Disordered Loop from Plasmodium falciparum Purine Nucleoside Phosphorylase: Involvement in Catalysis and Microenvironment

Among various tropical diseases, malaria is a major life-threatening disease caused by Plasmodium parasite. Plasmodium falciparum is responsible for the deadliest form of malaria, so-called cerebral malaria. Purine nucleoside phosphorylase from P. falciparum is a homohexamer containing single tryptophan residue per subunit that accepts inosine and guanosine but not adenosine for its activity. This enzyme has been exploited as drug target against malaria disease. It is important to draw together significant knowledge about inherent properties of this enzyme which will be helpful in better understanding of this drug target. The enzyme shows disorder to order transition during catalysis. The single tryptophan residue residing in conserved region of transition loop is present in purine nucleoside phosphorylases throughout the Plasmodium genus. This active site loop motif is conserved among nucleoside phosphorylases from apicomplexan parasites. Modification of tryptophan residue by N-bromosuccinamide resulted in complete loss of activity showing its importance in catalysis. Inosine was not able to protect enzyme against N-bromosuccinamide modification. Extrinsic fluorescence studies revealed that tryptophan might not be involved in substrate binding. The tryptophan residue localised in electronegative environment showed collisional and static quenching in the presence of quenchers of different polarities.     

Solvent dependent growth of fibrous and non-fibrous nanocrystalline thin films of ZnO

Zinc oxide thin films were prepared from three different solvents using the sol–gel technique. Zinc acetate was used as the source of Zn, and the solvents ethanol, 2-methoxy ethanol and ethylene glycol were used to prepare the sols. ZnO thin films were deposited on glass microslides by pre-heating dip coated sol layers, following which they were finally annealed at 450 °C for half an hour. The films were characterized using structural, morphological and optical techniques. XRD studies show that the films grown from all the three solvents were single phase, highly oriented (along the c axis) ZnO having the wurzite structure. Optical transmission and photoluminescence spectra confirm the good quality of the ZnO films. SEM and AFM images show that the surfaces of the ZnO films, obtained using the first two (more volatile) solvents, consist of striations or ridges of height around 100–400 nm and are made up of nanoparticles 20–40 nm in size. The surfaces of the films produced from the less volatile third solvent are however smooth and devoid of striations although they are also covered with nanoparticles.     

Liquid-phase microextraction based on solidified floating drops of organic solvents

Microextraction of organic or inorganic analytes using solidified floating drops of organic solvents is a fairly new method that is simple and rapid, and requires only small quantities of solvents and reagents. This review (with 109 references) covers published work up to Sep. 2012, and describes how the method was combined with analytical techniques such as GC, HPLC, ICP-OES and electrothermal atomic absorption spectrometry. We discuss basic principles and the main parameters that affect the extraction efficiency, and give specific applications of the technique.

2-Phenylindole derivatives as anticancer agents: synthesis and screening against murine melanoma,human lung and breast cancer cell lines

Indole derivatives have attractive anticancer properties and may be a future hope for better anticancer drug(s) of low toxicity and high potency. In this paper, syntheses of 2-phenylindole derivatives have been described via Fischer indole synthesis through a one-pot solvent-free method. The synthesized compounds were screened for anticancer potential in vitro against murine melanoma (B16F10), human lung cancer (A549), and human breast cancer (MDA-MB-231) cell lines. The results highlighted that 2-phenylindole derivatives are also promising anticancer agents in case of melanoma and lung cancer along with the breast cancer. Molecular docking analyses with possible targets for melanoma (NEDD4-1) and lung cancer (EGFR) were also performed to understand specific interactions of 2-phenylindole derivatives with the amino acid residues of the receptors.     

Design and Synthesis of Benzimidazole-Linked meta-Substituted Benzylidenes/Benzyls as Biologically Significant New Chemical Entities

meta-Linked thiazolidinedione (TZD)– and diethyl malonate (DEM)–based benzylidenes and methyl acetoacetate (MAA)–based benzyl moieties linked to the 2-position of N-methyl benzimidazole were synthesized. TZD- and DEM-based compounds were synthesized by condensation of 2,4-thiazolidinedone and DEM respectively with the corresponding 3-substituted benzaldehyde, whereas MAA-based compounds were obtained by halogen displacement with the corresponding 3-substituted phenol. These new chemical entities were designed to provide a balanced agonism at the peroxisome proliferator activated receptor alpha/gamma (PPARα/γ) in the management of type 2 diabetes: a move from glitazones to selective PPARγ modulators (SPPARγMs).

Supplemental materials are available for this article. Go to the publisher's online edition of Synthetic Communications® to view the free supplemental file.     

A phosgene and peroxide-free one-pot tandem synthesis of isatoic anhydrides involving anthranilic acid,Boc anhydride,and 2-chloro-N-methyl pyridinium iodide

A phosgene and peroxide-free approach for the synthesis of isatoic anhydrides has been described. The synthesis involves the carbamate formation with Boc anhydride followed by in situ cyclization to afford the isatoic anhydride. The importance of this synthetic strategy is in the ease of operation, scalability, and preparation from readily available raw materials.     

Thiourea dioxide promoted efficient organocatalytic one-pot synthesis of a library of novel heterocyclic compounds

The utility of thiourea dioxide as an efficient organocatalyst for the library synthesis of novel heterocyclic compounds via one-pot multicomponent coupling reactions is disclosed. Thiourea dioxide is an inexpensive and readily accessible catalyst, resulting in better product yields as compared to the corresponding thiourea as catalyst. Thiourea dioxide is found to be insoluble in various organic solvents and therefore at the end of the reaction products can be separated by extraction with diethyl ether and the recovered catalyst can be used several times with consistent catalytic activity.     

Base-mediated regio- and stereoselective intermolecular addition of alkynes to N-heterocycles

The regio- and stereoselective addition of N-heterocycles to alkynes using KOH is reported. Formation of (Z)-isomers and their conversion to (E)-products were found to be dependent upon time as well as the choice of base. Selective attack of N-heterocycles on a more electrophilic alkynyl carbon was supported by DFT calculations, and the stereochemistry of the products was established by X-ray crystallographic studies and intramolecular cyclization of ortho-haloalkynes in indolo-[2,1-a]isoquinolines.