Metabolomics for characterization of gender differences in patients infected with dengue virus

Objective:To determine the metabolic response associate with dengue infection based on human gender metabolic differences by means of ~1H NMR-spectrometry.Methods:The mid-stream urine collected from both male and female patients diagnosed with dengue fever at Penang General Hospital and fourty-three healthy individuals were analyzed with^1H NMR spectroscopy,followed by chemometric multivariate analysis.NMR signals which highlighted in the OPLS-DA S-plot were further selected and identified using Human Metabolome Database,Chenonix Profiler.Results:The results pointed out that NMR urine profiling was able to capture human gender metabolic differences that are important for the distinction of classes of individuals of similar physiological conditions;infected with dengue.Distinct differences between dengue infected patients versus healthy individuals and subtle differences in male versus female infected with dengue were found to be related to the metabolism of amino acid and tricarboxylic acid intermediates cycle.Conclusions:The ~1H NMR metabolomic investigation combined with appropriate algorithms and pattern recognition procedures,gave an evidence for the existence of distinct metabolic differentiation of individuals,according to their gender,modulates with the infection risk.

The Uptake of Copper(II) Ions by Chelating Schiff Base Derived from 4-Aminoantipyrine and 2-Methoxybenzaldehyde

The Schiff base, 4-[(2-methoxybenzylidene)amino]-1,5-dimethyl-2-phenyl-1H-pyrizol-3(2H)-one (SB), was used for the first time to adsorb copper(II) ions in aqueous solution. Various parameters such as initial pH, agitation period and different initial concentration of copper(II) ions which influenced the adsorption capacity were investigated. The equilibrium adsorption data for copper(II) ions were fitted to Langmuir, Freundlich and Dubinin-Radushkevish isotherm models. The maximum monolayer adsorption capacity of SB as obtained from Langmuir isotherm was 5.64 mg/g. Kinetic data correlated well with the pseudo second-order kinetic model indicating that chemical adsorption was the rate limiting step.

3,5-Bis(arylidene)-4-piperidones as potential dengue protease inhibitors

Dengue is a severe mosquito-borne viral infection causing half a million deaths annually.Dengue virus NS2B/NS3 protease is a validated target for anti-dengue drug design. A series of hitherto unreported 3,5-bis(arylidene)-4-piperidones analogues 4a–4j were synthesized and screened in silico against DENV2 NS2B/NS3 protease to elucidate their binding mechanism and orientation around the active sites. Results were validated through an in vitro DENV2 NS2B/NS3 protease assay using a fluorogenic Boc-Gly-Arg-Arg-AMC substrate. Nitro derivatives of 3,5-bis(arylidene)-4-piperidones(4e and 4j) emerged as promising lead molecules for novel protease inhibitors with an IC50 of 15.22 and16.23 mmol/L, respectively, compared to the standard, panduratin A, having IC50 of 57.28 mmol/L.