Nornisah Mohamed

Xanthine oxidase inhibitory activities of extracts and flavonoids of the leaves of Blumea balsamifera

Context: Blumea balsamifera DC (Compositae) leaves have been recommended for use as a folk medicine in the treatment of various diseases related to urolithiasis in southeast Asia. Phytochemical studies of this plant revealed it contains four classes of flavonoids (e.g., flavonols, flavones, flavanones, and dihydroflavonol derivatives). Objective: In view of the broad pharmacological activity of flavonoids, this study was carried out to determine the xanthine oxidase (XO) inhibitory and enzymatically produced superoxide radical scavenging activity of different organic extracts and that of the isolated flavonoids from B. balsamifera leaves. Materials and methods: The inhibitory activity of XO was assayed spectrophotometrically at 295 nm. The superoxide radicals scavenging activity was assessed by NBT reduction method, spectrophotometrically at 560 nm. A dose response curve was plotted for determining IC50 values. Results: The methanol extract (IC50 = 0.111 mg/mL) showed higher XO inhibitory activity than the chloroform (0.138 mg/mL) and pet-ether extracts (0.516 mg/mL). IC50 values of scavenging of superoxide radicals for extracts decreased in the order of: methanol (0.063 mg/mL) > chloroform (0.092 mg/mL) > pet-ether (0.321 mg/mL). The XO inhibitory activity of the isolated flavonoids and reference compounds tested decreased in the order of: allopurinol > luteolin > quercetin > tamarixetin > 5,7,3′,5′-tetrahydroxyflavanone > rhamnetin > luteolin-7-methyl ether > blumeatin > dihydroquercetin-4′-methyl ether > dihydroquercetin-7,4′-dimethyl ether > l-ascorbic acid. Discussion and conclusion: The results indicated that the flavone derivatives were more active than the flavonol derivatives. The flavanone derivatives were moderately active and the dihydroflavonol derivatives were the least. The higher flavonoid content of extracts contributed to their higher XO inhibitory activity.

A virtual screening approach for identifying plants with anti H5N1 neuraminidase activity

Recent outbreaks of highly pathogenic and occasional drug-resistant influenza strains have highlighted the need to develop novel anti-influenza therapeutics. Here, we report computational and experimental efforts to identify influenza neuraminidase inhibitors from among the 3000 natural compounds in the Malaysian-Plants Natural-Product (NADI) database. These 3000 compounds were first docked into the neuraminidase active site. The five plants with the largest number of top predicted ligands were selected for experimental evaluation. Twelve specific compounds isolated from these five plants were shown to inhibit neuraminidase, including two compounds with IC50 values less than 92 μM. Furthermore, four of the 12 isolated compounds had also been identified in the top 100 compounds from the virtual screen. Together, these results suggest an effective new approach for identifying bioactive plant species that will further the identification of new pharmacologically active compounds from diverse natural-product resources.

Potential New H1N1 Neuraminidase Inhibitors from Ferulic Acid and Vanillin: Molecular Modelling, Synthesis and in Vitro Assay

We report the computational and experimental efforts in the design and synthesis of novel neuraminidase (NA) inhibitors from ferulic acid and vanillin. Two proposed ferulic acid analogues, MY7 and MY8 were predicted to inhibit H1N1 NA using molecular docking. From these two analogues, we designed, synthesised and evaluated the biological activities of a series of ferulic acid and vanillin derivatives. The enzymatic H1N1 NA inhibition assay showed MY21 (a vanillin derivative) has the lowest IC50 of 50 μM. In contrast, the virus inhibition assay showed MY15, a ferulic acid derivative has the best activity with the EC50 of ~0.95 μM. Modelling studies further suggest that these predicted activities might be due to the interactions with conserved and essential residues of NA with ΔGbind values comparable to those of oseltamivir and zanamivir, the two commercial NA inhibitors.

H274Y’s Effect on Oseltamivir Resistance: What Happens Before the Drug Enters the Binding Site

Increased reports of oseltamivir (OTV)-resistant strains of the influenza virus, such as the H274Y mutation on its neuraminidase (NA), have created some cause for concern. Many studies have been conducted in the attempt to uncover the mechanism of OTV resistance in H274Y NA. However, most of the reported studies on H274Y focused only on the drug-bound system, so the direct effects of the mutation on NA itself prior to drug binding still remain unclear. Therefore, molecular dynamics simulations of NA in apo form, followed by principal component analysis and interaction energy calculations, were performed to investigate the structural changes of the NA binding site as a result of the H274Y mutation. It was observed that the disruption of the NA binding site due to the H274Y mutation was initiated by the repulsive effect of Y274 on the 250-loop, which in turn altered the hydrogen-bonding network around residue 274. The rotated W295 side chain caused the upward movement of the 340-loop. Consequently, sliding box docking results suggested that the binding pathway of OTV was compromised because of the disruption of this binding site. This study also highlighted the importance of the functional group at C6 of the sialic acid mimicry. It is hoped that these results will improve the understanding of OTV resistance and shed some light on the design of a novel anti-influenza drug.

Diaqua­bis­(hydrogen tartrato)copper(II) dihydrate

The title complex, [Cu(C4H5O6)2(H2O)2]·2H2O, contains a CuII ion lying on an inversion centre. The coordination geometry of the CuII ion is a distorted octahedron with four O atoms from two hydrogen tartrate ions occupying the equatorial positions and two O atoms from two coordinated water molecules occupying the axial positions. In the crystal structure, intermolecular O—H⋯O and C—H⋯O hydrogen bonds link the molecules into a three-dimensional network.

Tetra­kis(2,6-diamino­pyridinium) diphthalate 2,6-diamino­pyridine

In the title compound, 4C5H8N3 +·2C8H4O4 2−·C5H7N3, the asymmetric unit consists of two protonated diaminopyridine cations, one phthalate anion and one half of a diaminopyridine molecule, which has twofold rotation symmetry and is disordered over two positions with a site-occupancy ratio of 0.534 (3):0.466 (3). In the disordered structure, both pyridine rings are essentially planar, with maximum deviations of 0.011 (2) and 0.006 (2) Å, and these two rings are inclined to one another at a dihedral angle of 79.86 (10)°. In the crystal structure, intermolecular N—H⋯O and C—H⋯O hydrogen bonds link the ions and molecules into a three-dimensional network. The structure is further stabilized by C—H⋯π interactions.

4-(3,4-Dimethyl-5-phenyl-1,3-oxazolidin-2-yl)-2-methoxy­phenol

In the title compound, C18H21NO3, the oxazolidine ring adopts an envelope conformation with the N atom at the flap position. The two benzene rings make dihedral angles of 74.27 (14) and 73.26 (15)° with the mean plane through the oxazolidine ring. In the crystal structure, O—H⋯O and C—H⋯O hydrogen bonds connect adjacent molecules into chains along [010] incorporating R 2 2(8) loops and further stabilization is provided by weak intermolecular C—H⋯π interactions.

2,6-Diamino­pyridinium 2-carb­oxy­benzoate

In the crystal of the title molecular salt, C5H8N3 +·C8H5O4 −, the diaminopyridine cation and the phthalate anion are linked by a pair of N—H⋯O hydrogen bonds. Within the phthalate anion, an almost symmetrical O—H⋯O hydrogen bond is observed. The ion pairs are linked by further N—H⋯O hydrogen bonds, generating a two-dimensional network lying parallel to (10).

Monoclinic polymorph of poly[aqua(μ4-hydrogen tartrato)sodium]

A monoclinic polymorph of the title compound, [Na(C4H5O6)(H2O)]n, is reported and complements an orthorhombic form [Kubozono, Hirano, Nagasawa, Maeda & Kashino (1993 ▶). Bull. Chem. Soc. Jpn, 66, 2166–2173]. The asymmetric unit contains a hydrogen tartrate anion, an Na+ cation and a water molecule. The Na+ ion is surrounded by seven O atoms derived from one independent and three symmetry-related hydrogen tartrate anions, and a water molecule, forming a distorted pentagonal–bipyramidal geometry. Independent units are linked via a pair of intermolecular bifurcated O—H⋯O acceptor bonds, generating an R 2 1(6) ring motif to form polymeric two-dimensional arrays parallel to the (100) plane. In the crystal packing, the arrays are linked by adjacent ring motifs, together with additional intermolecular O—H⋯O interactions, into a three-dimensional network.

Tetra­guanidinium bis­[citrato(3−)]cuprate(II) dihydrate

The asymmetric unit of the title compound, (CH6N3)4[Cu(C6H5O7)2]·2H2O, contains one-half of a centrosymmetric CuII complex anion, two guanidinium cations and a water molecule. The CuII ion, lying on a crystallographic inversion center, is hexacoordinated with two citrate anions in a distorted octahedral geometry. An intramolecular O—H⋯O hydrogen bond generates an S(6) ring motif. In the crystal structure, molecules are linked into a three-dimensional framework by intermolecular N—H⋯O and O—H⋯O hydrogen bonds.