Sharifuddin Md. Zain

Design of New Competitive Dengue Ns2b/Ns3 Protease Inhibitors—A Computational Approach

Dengue is a serious disease which has become a global health burden in the last decade. Currently, there are no approved vaccines or antiviral therapies to combat the disease. The increasing spread and severity of the dengue virus infection emphasizes the importance of drug discovery strategies that could efficiently and cost-effectively identify antiviral drug leads for development into potent drugs. To this effect, several computational approaches were applied in this work. Initially molecular docking studies of reference ligands to the DEN2 NS2B/NS3 serine protease were carried out. These reference ligands consist of reported competitive inhibitors extracted from Boesenbergia rotunda (i.e., 4-hydroxypanduratin A and panduratin A) and three other synthesized panduratin A derivative compounds (i.e., 246DA, 2446DA and 20H46DA). The design of new lead inhibitors was carried out in two stages. In the first stage, the enzyme complexed to the reference ligands was minimized and their complexation energies (i.e., sum of interaction energy and binding energy) were computed. New compounds as potential dengue inhibitors were then designed by putting various substituents successively on the benzyl ring A of the reference molecule. These substituted benzyl compounds were then computed for their enzyme-ligand complexation energies. New enzyme-ligand complexes, exhibiting the lowest complexation energies and closest to the computed energy for the reference compounds, were then chosen for the next stage manipulation and design, which involved substituting positions 4 and 5 of the benzyl ring A (positions 3 and 4 for 2446DA) with various substituents.

Antimicrobial Activity of Novel Synthetic Peptides Derived from Indolicidin and Ranalexin against Streptococcus pneumoniae.

Antimicrobial peptides (AMPs) represent promising alternatives to conventional antibiotics in order to defeat multidrug-resistant bacteria such as Streptococcus pneumoniae. In this study, thirteen antimicrobial peptides were designed based on two natural peptides indolicidin and ranalexin. Our results revealed that four hybrid peptides RN7-IN10, RN7-IN9, RN7-IN8, and RN7-IN6 possess potent antibacterial activity against 30 pneumococcal clinical isolates (MIC 7.81-15.62µg/ml). These four hybrid peptides also showed broad spectrum antibacterial activity (7.81µg/ml) against S. aureus, methicillin resistant S. aureus (MRSA), and E. coli. Furthermore, the time killing assay results showed that the hybrid peptides were able to eliminate S. pneumoniae within less than one hour which is faster than the standard drugs erythromycin and ceftriaxone. The cytotoxic effects of peptides were tested against human erythrocytes, WRL-68 normal liver cell line, and NL-20 normal lung cell line. The results revealed that none of the thirteen peptides have cytotoxic or hemolytic effects at their MIC values. The in silico molecular docking study was carried out to investigate the binding properties of peptides with three pneumococcal virulent targets by Autodock Vina. RN7IN6 showed a strong affinity to target proteins; autolysin, pneumolysin, and pneumococcal surface protein A (PspA) based on rigid docking studies. Our results suggest that the hybrid peptides could be suitable candidates for antibacterial drug development.

Distribution and health risk assessment of trace metals in freshwater tilapia from three different aquaculture sites in Jelebu Region (Malaysia).

The trace metal concentrations in edible muscle of red tilapia (Oreochromis spp.) sampled from a former tin mining pool, concrete tank and earthen pond in Jelebu were analysed with microwave assisted digestion-inductively coupled plasma-mass spectrometry. Results were compared with established legal limits and the daily ingestion exposures simulated using the Monte Carlo algorithm for potential health risks. Among the metals investigated, arsenic was found to be the key contaminant, which may have arisen from the use of formulated feeding pellets. Although the risks of toxicity associated with consumption of red tilapia from the sites investigated were found to be within the tolerable range, the preliminary probabilistic estimation of As cancer risk shows that the 95th percentile risk level surpassed the benchmark level of 10(-5). In general, the probabilistic health risks associated with ingestion of red tilapia can be ranked as follows: former tin mining pool > concrete tank > earthen pond.

Magnetic solid phase extraction of polycyclic aromatic hydrocarbons and chlorophenols based on cyano-ionic liquid functionalized magnetic nanoparticles and their determination by HPLC-DAD

A magnetic solid-phase extraction (MSPE) procedure on the newly synthesized cyano-ionic liquid functionalized magnetic nanoparticles (MNP@CN/IL) was established and validated for the separation/preconcentration of polycyclic aromatic hydrocarbons (PAHs) and chlorophenols (CPs) from water samples prior to their HPLC-DAD determination. The new magnetic (MNP@CN/IL) adsorbent was characterized by Fourier transform infrared (FT-IR) spectroscopy, X-ray diffraction (XRD), elemental analysis (CHNS), energy-dispersive X-ray spectroscopy (EDX), vibrating sample magnetometry (VSM), thermal gravimetric analysis (TGA) and transmission electron microscopy (TEM). The proposed method showed preconcentrations of 200 and 100 with low limits of detection (LOD = 0.40–0.59 and 0.35–0.67 μg L−1) with linearity ranges from 0.1–100 and 3–100 μg L−1 for PAHs and CPs, respectively. The extraction recoveries from environmental samples (leachate and sludge from a landfill site) ranged from 89.50–110.2% and 80.67–112.7% for PAHs and CPs, respectively, with satisfactory precision (% RSD less than 5%). The combination of cyano group and ionic liquid on the surface of the MNPs enhanced the extraction efficiency which might be due to π–π interactions as well as electrostatic interactions.

Evaluation of microwave-assisted digestion condition for the determination of metals in fish samples by inductively coupled plasma mass spectrometry using experimental designs

This paper describes the development of a compromised single-stage microwave-assisted digestion condition for multi-element determination in fish samples by inductively coupled plasm: mass spectrometry using experimental designs. A Plackett–Burman design was carried out as a multivariate strategy to investigate the main effects of the following parameter on microwave-assisted nitric acid digestion: microwave irradiation time, ramp time, digestion temperature, microwave power limit and the addition of hydrogen peroxide or hydrochloric acid. The most significant microwave setting parameters (radiation time, ramp and temperature) were further evaluated by response surface methodology under Box–Behnken design, while others were kept constant. The influences of different parameters vary according to metal element, thus the working conditions were established as a compromise within optimum region found for each targeted element which ensures quantitative recoveries and time efficiency. The compromised conditions are: ramp to 185°C in 10.5 min then hold for 14.5 min with 1600W (50%) of microwave power, using reagent mixture composed of 2.5 mL nitric acid, 0.5 mL hydrochloric acid and 7.0 mL water. Good agreements were demonstrated between measured and certified values with respect to DORM-3, DOLT-4 and ECM-CE278 and this method was successfully applied for metals determination in tilapia tissues.

Spatial assessment and source identification of heavy metals pollution in surface water using several chemometric techniques.

UNLABELLED This study presents the determination of the spatial variation and source identification of heavy metal pollution in surface water along the Straits of Malacca using several chemometric techniques. Clustering and discrimination of heavy metal compounds in surface water into two groups (northern and southern regions) are observed according to level of concentrations via the application of chemometric techniques. Principal component analysis (PCA) demonstrates that Cu and Cr dominate the source apportionment in northern region with a total variance of 57.62% and is identified with mining and shipping activities. These are the major contamination contributors in the Straits. Land-based pollution originating from vehicular emission with a total variance of 59.43% is attributed to the high level of Pb concentration in the southern region. The results revealed that one state representing each cluster (northern and southern regions) is significant as the main location for investigating heavy metal concentration in the Straits of Malacca which would save monitoring cost and time. CAPSULE The monitoring of spatial variation and source of heavy metals pollution at the northern and southern regions of the Straits of Malacca, Malaysia, using chemometric analysis.

A novel cyano functionalized silica-titania oxide sol–gel based ionic liquid for the extraction of hazardous chlorophenols from aqueous environments

In the present investigation a cyano functionalized silica-titania oxide sol–gel based ionic liquid (Si-Ti@CN/IL) has been successfully synthesised via sol–gel immobilization of cyanopropyltriethoxysilane and 1-benzyl-3-(trimethoxysilylpropyl)imidazolium chloride ionic liquid (BTMP-IM) on the silica-titania mixed oxide surface. The newly prepared Si-Ti@CN/IL was used as an adsorbent for the separation/preconcentration of chlorophenols from water samples prior to their HPLC-UV determination. Synthesis of Si-Ti@CN/IL was confirmed by Fourier transform infrared (FT-IR) spectroscopy, field emission scanning electron microscopy (FESEM), Brunauer–Emmett–Teller (BET), thermo gravimetric analysis (TGA), X-ray diffraction (XRD) and elemental (CHNS) analysis. During the extraction process, various kinds of interactions such as π–π interactions and hydrogen bonding between the anionic/cationic sites were monitored. The extraction of chlorophenols on Si-Ti@CN/IL is highly pH dependent and a significant percent extraction was achieved at pH = 2. The Si-Ti@CN/IL provided low limit of detection (LOD = 0.83–0.95 μg L−1) with a linearity range from 10–1000 μg L−1 (LOQ = 2.77–3.17 μg L−1). The field studies with high recovery (73.39–105.54%) as well as acceptable precision (%RSD 0.82–4.19) also supported the effectiveness of Si-Ti@CN/IL, which could be useful for the extraction of selected chlorophenols from tap water, lake water and leachate from landfill sites. The comparative data support Si-Ti@CN/IL as an effective extractant for selected chlorophenols.

Improved scFv anti-HIV-1 p17 binding affinity guided from the theoretical calculation of pairwise decomposition energies and computational alanine scanning.

Computational approaches have been used to evaluate and define important residues for protein-protein interactions, especially antigen-antibody complexes. In our previous study, pairwise decomposition of residue interaction energies of single chain Fv with HIV-1 p17 epitope variants has indicated the key specific residues in the complementary determining regions (CDRs) of scFv anti-p17. In this present investigation in order to determine whether a specific side chain group of residue in CDRs plays an important role in bioactivity, computational alanine scanning has been applied. Molecular dynamics simulations were done with several complexes of original scFv anti-p17 and scFv anti-p17mutants with HIV-1 p17 epitope variants with a production run up to 10 ns. With the combination of pairwise decomposition residue interaction and alanine scanning calculations, the point mutation has been initially selected at the position MET100 to improve the residue binding affinity. The calculated docking interaction energy between a single mutation from methionine to either arginine or glycine has shown the improved binding affinity, contributed from the electrostatic interaction with the negative favorably interaction energy, compared to the wild type. Theoretical calculations agreed well with the results from the peptide ELISA results.

Chemometric techniques in oil classification from oil spill fingerprinting

Extended use of GC-FID and GC-MS in oil spill fingerprinting and matching is significantly important for oil classification from the oil spill sources collected from various areas of Peninsular Malaysia and Sabah (East Malaysia). Oil spill fingerprinting from GC-FID and GC-MS coupled with chemometric techniques (discriminant analysis and principal component analysis) is used as a diagnostic tool to classify the types of oil polluting the water. Clustering and discrimination of oil spill compounds in the water from the actual site of oil spill events are divided into four groups viz. diesel, Heavy Fuel Oil (HFO), Mixture Oil containing Light Fuel Oil (MOLFO) and Waste Oil (WO) according to the similarity of their intrinsic chemical properties. Principal component analysis (PCA) demonstrates that diesel, HFO, MOLFO and WO are types of oil or oil products from complex oil mixtures with a total variance of 85.34% and are identified with various anthropogenic activities related to either intentional releasing of oil or accidental discharge of oil into the environment. Our results show that the use of chemometric techniques is significant in providing independent validation for classifying the types of spilled oil in the investigation of oil spill pollution in Malaysia. This, in consequence would result in cost and time saving in identification of the oil spill sources.

Bis(dicyclohexylammonium 4-hydroxy-benzoate)

In the crystal structure of the title compound, 2C(12)H(24)N(+)center dot 2C(7)H(5)O(3)(-), the cation is linked to the single-bonded carboxylate O atom of an anion as well as to the double-bonded carbonyl O atom of another anion to form a centrosymmetric hydrogen-bonded ion pair. Adjacent ion pairs are linked through the hydroxy group of the anion to produce a honeycomb-like layer structure.