PIFA–BF3·OEt2 mediated intramolecular regioselective domino cyclization of ynamides: A novel method for the synthesis of tetrahydroisoquinoline-oxazol-2(3H)-ones

The transition metal-free intramolecular regioselective domino cyclization of N-Boc protected ynamides has been developed to provide the corresponding tetrahydroisoquinoline-oxazo-2(3H)-ones in moderate to good yields.     

Structural and Dynamical Properties of a Full-length HIV-1 Integrase: Molecular Dynamics Simulations

Abstract

The structural and dynamical properties of the complete full-length structure of HIV-1 integrase were investigated using Molecular Dynamics approach. Simulations were carried out for the three systems, core domain only (CORE), full-length structure without (FULL) and with a Mg²⁺ (FULL+ION) in its active site, aimed to investigate the difference in the molecular properties of the full-length models due to their different construction procedures as well as the effects of the two ends, C- and N-terminal, on those properties in the core domain. The full-length structure was prepared from the two experimental structures of two-domain fragment. The following properties were observed to differ significantly from the previous reports: (i) relative topology formed by an angle between the three domains; (ii) the cavity size defined by the catalytic triad, Asp64, Asp116, and Glul52; (iii) distances and solvation of the Mg²⁺; and (iv) conformation of the catalytic residues. In addition, the presence of the two terminal domains decreases the mobility of the central core domain significantly.     

Three new species of the carnivorous snail genus Perrottetia Kobelt, 1905 from Thailand (Pulmonata,?Streptaxidae)

Three new species of the streptaxid snail genus Perrottetia are described from north and northeastern Thailand, Perrottetia aquilonaria sp. n., Perrottetia dermapyrrhosa sp. n. and Perrottetia phuphamanensis sp. n. Each species is endemic to a single or a few limestone mountain ranges. The species are characterized by the morphology of their genital organs, as well as by shell characters. Perrottetia aquilonaria sp. n. has a club shaped distal penis and large penial hooks are present and penial papillae cover almost the entire penial hook portion; adjacent areas possess low reticulated folds. Perrottetia dermapyrrhosa sp. n. has a long genital atrium and the penial sheath is about two-thirds of the penis length. Penial hooks are long, scattered and sunken into deep ovate hollows; vaginal hooks are present. Perrottetia phuphamanensis sp. n. has a rounded and protruded shell periphery. The aperture is subcircular, peristome is thick and the second parietal lamella is adjacent to the first parietal lamella; a basal lamella is the smaller than in the other Thai species.     

Investigation of some bioactive Thai medicinal plants

It has been estimated that plants are the most important source of medicine for more than 80% of the world’s population. Medicinal plants are a vital source of medication in developing countries. Despite the wealth of human experience and folklore concerning the medicinal uses of plants, proper scientific investigation has only been applied to a small fraction of the world’s plants. This is a cause of grave concern as plant species continue to disappear. A rapid response to this situation is urgently needed to prevent the disappearance of the plant species and the ethnopharmacological knowledge that accompanies them. In this review, recent work on the investigation of selected bioactive Thai medicinal plants is presented. Their biological activities against infectious diseases including antimalarial and anti-HIV, are highlighted, as well as their anticancer, antiulcer and anti-inflammatory properties. The chemical transformations of some selected compounds are discussed. This revised version was published online in June 2006 with corrections to the Cover Date.     

The C-terminal region of xylanase domain in Xyn11A from Paenibacillus curdlanolyticus B-6 plays an important role in structural stability

Paenibacillus curdlanolyticus B-6 produces an extracellular multienzyme complex containing a major xylanase subunit, designated Xyn11A, which includes two functional domains belonging to glycosyl hydrolase family-11 (GH11) and carbohydrate binding module family-36 (CBM36) and possesses a glycine and asparagine-rich linker (linker). To clarify the roles of each functional domain, recombinant proteins XynXL and XynX (CBM36 deleted and CBM36 and linker deleted, respectively) were constructed. Their xylanase activities were similar toward soluble xylan, whereas XynXL showed decreased hydrolysis activity toward insoluble xylan while XynX had no xylanase activity. To determine the significance of the linker and its neighbor region, XynX was subjected to secondary structural alignments using circular dichroism (CD) spectroscopy and three-dimensional (3D) structural analysis. A seven amino acid (NTITIGG) neighbor linker sequence was highly conserved among GH11 xylanases of Paenibacillus species. Although XynX exhibited a typical GH11 xylanase structure, conformational gaps were observed in the β6- and β12-sheets and in CD spectra. Flipping of the Arg163 side chains in the subsite was also observed upon analysis of superimposed models. Docking analysis using xylohexaose indicated that flipping of the Arg163 side chains markedly affected substrate binding in the subsite. To identify the amino acids related to stabilizing the substrate binding site, XynX with an extended C-terminal region was designed. At least seven amino acids were necessary to recover substrate binding and xylanase activity. These results indicated that the seven amino acid neighbor Xyn11A linker plays an important role in the activity and conformational stability of the xylanase domain.     

Molecular dynamics simulation,binding free energy calculation and molecular docking of human D-amino acid oxidase (DAAO) with its inhibitors

Schizophrenia is a mental illness; most affected people live in developing countries, and neither appropriate treatment nor commercial drugs are currently available. One possibility is to inhibit human-d-amino acid oxidase (h-DAAO). In this study, molecular dynamic simulations of the monomer, dimer and tetramer forms of h-DAAO complexed with the inhibitor 3-hydroxyquinolin-2(1H)-one(2) were performed. Seven residues, Leu51, Gln53, Leu215, Tyr228, Ile230, Arg283 and Gly313, were identified as essential for interacting with the inhibitor. Molecular docking of h-DAAO with pyrrole, quinoline and kojic acid derivatives, representing 69 known or potential h-DAAO inhibitors, was also performed. The results indicated that the activity of the inhibitor can be improved by modifying the compounds to have a substituent group capable of interacting with the side chain of Tyr228. Van der Waals interactions of the inhibitor with the hydrophobic pocket of h-DAAO and electrostatic interactions or H-bonds with Arg283 and Gly313 were important elements in determining the efficiency of the inhibitor. These results provide information on the interaction between h-DAAO and its inhibitors at the molecular level and can aid in the design of novel inhibitors against h-DAAO for new drug development in the treatment of schizophrenia.     

Heavy metal accumulation in aquatic animals around the gold mine area of Loei province,Thailand

This research was conducted to assess the water quality and the contamination of heavy metals in water, sediment, fish, and frogs, as well as bioaccumulation factors (BAFs) in fish and frogs around the gold mine area. The water samples were analyzed for water quality (temperature, pH, and dissolved oxygen). The samples were analyzed for heavy metals by inductively coupled plasma optical emission spectrometry. The water quality was within the standard. The concentrations of heavy metals, including As, Cr, Cd, Pb, Ni, Zn, Fe, Mn, and Cu, in water and sediment samples were measured. Three species of fish were collected: Rasbora tornieri, Brachydanio albolineata, and Systomus rubripinnis. The mean heavy metal concentrations of fish were as follows: Fe>Zn>Mn>Cr>Ni>Cu>As>Pb>Cd. The As, Cr, and Pb concentrations in all the fish species exceeded the standard levels. Five species of frogs were collected: Kaloula pulchra, Microhyla heymonsi, Fejervarya limnocharis, Hoplobatrachus rugulosus, and Microhyla pulchra. The mean heavy metal concentrations of frog were as follows: Fe>Cu>Mn>Zn>Cr>Ni>Pb>Cd>As. The Cr, Cd, and Cu concentrations exceeded the standard levels. The BAFs in fish were in order of Cr>Zn>Ni>Cu>Pb>Fe>Cd>As. The BAFs in frogs were Cr>Zn>Ni>Cu>Fe>Pb>Cd>As. The accumulation of heavy metals was higher in the sediment than in the water. Many aquatic organisms take up heavy metals directly from the environment around the gold mine.