1HNMR-Based Discriminatory Analysis of Eurycoma longifolia from Different Locations and Establishing a Profile for Primary Metabolites Identification and Quassinoids Quantification.

Quassinoids, the major secondary metabolites of Eurycoma longifolia roots, improve male fertility. Hence, it is crucial to investigate their quantitative level in E. longifolia extracts. A profile was established to identify the primary metabolites and major quassinoids, and quantify quassinoids using external calibration curves. Furthermore, the metabolic discrimination of E. longifolia roots from different regions was investigated. The 1H-NMR spectra of the quassinoids, eurycomanone, eurycomanol, 13,21-dihydroeurycomanone, and eurycomanol-2-O-ß-D-glycopyranoside were obtained. The 1H-NMR profiles of E. longifolia root aqueous extracts from Perak (n = 30) were obtained and used to identify primary metabolites and the quassinoids. Selangor, Kedah, Terengganu (n = 5 for each), and Perak samples were checked for metabolic discrimination. Hotelling's T2 plot was used to check for outliers. Orthogonal partial least-squares discriminant analysis was run to reveal the discriminatory metabolites. Perak samples contained formic, succinic, methylsuccinic, fumaric, lactic, acetic and syringic acids as well as choline, alanine, phenylalanine, tyrosine, α-glucose, eurycomanone, eurycomanol, 13,21-dihydroeurycomanone, and eurycomanol-2-O-ß-D-glycopyranoside. The extracts from other locations contained the same metabolites. The limit of quantification values were 1.96 (eurycomanone), 15.62 (eurycomanol), 3.91 (13,21-dihydroeurycomanone), and 31.25 (eurycomanol-2-O-ß-D-glycopyranoside) ppm. The Hotelling's T2 plot revealed no outlier. The orthogonal partial least-squares discriminant analysis model showed that choline, eurycomanol, eurycomanol-2-O-ß-D-glycopyranoside, and lactic and succinic acid levels were different among regions. Terengganu and Perak samples contained higher amounts of eurycomanol and eurycomanol-2-O-ß-D-glycopyranoside, respectively. The current approach efficiently detected E. longifolia root metabolites, quantified the quassinoids, and discriminated E. longifolia roots from different locations. These findings could be applicable to future research on E. longifolia where the higher content of quassinoids is required.

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.

Microwave-assisted synthesis and antioxidant properties of hydrazinyl thiazolyl coumarin derivatives.

BACKGROUND: Coumarin derivatives exhibit a wide range of biological properties including promising antioxidant activity. Furthermore, microwave-assisted organic synthesis has delivered rapid routes to N- and O-containing heterocycles, including coumarins and thiazoles. Combining these features, the use of microwave-assisted processes will provide rapid access to a targeted coumarin library bearing a hydrazino pharmacophore for evaluation of antioxidant properties RESULTS: Microwave irradiation promoted 3 of the 4 steps in a rapid, convergent synthesis of a small library of hydrazinyl thiazolyl coumarin derivatives, all of which exhibited significant antioxidant activity comparable to that of the natural antioxidant quercetin, as established by DPPH and ABTS radical assays CONCLUSIONS: Microwave dielectric heating provides a rapid and expedient route to a series of hydrazinyl thiazolyl coumarins to investigate their radical scavenging properties. Given their favourable properties, in comparison with known antioxidants, these coumarin derivatives are promising leads for further development and optimization.

(E)-6-Bromo-3-{2-[2-(2-meth-oxy-benzyl-idene)hydrazin-yl]-1,3-thia-zol-4-yl}-2H-chromen-2-one.

In the title compound, C(20)H(14)BrN(3)O(3)S, the mol-ecule adopts an E configuration about the central C=N double bond. The chromene ring system and the thia-zole ring are approximately planar [maximum deviations = 0.029 (3) and 0.007 (3) Å, respectively]. The chromene ring system is inclined at angles of 7.37 (12) and 13.90 (13)° with respect to the thia-zole and benzene rings, respectively, while the thia-zole ring makes a dihedral angle of 12.58 (15)° with the benzene ring. In the crystal, mol-ecules are connected by N-H⋯O hydrogen bonds, forming C(8) supra-molecular chains along the c axis.

(E)-6-Bromo-3-{2-[2-(4-chloro-benzyl-idene)hydrazin-yl]thia-zol-5-yl}-2H-chromen-2-one.

In the title compound, C(19)H(11)N(3)O(2)SClBr, the chromene ring system and the thia-zole ring are each approximately planar, with maximum deviations of 0.033 (3) Šand 0.006 (3) Å, respectively. The mol-ecule adopts an E configuration about the central C=N double bond. The central thia-zole ring makes dihedral angles of 9.06 (14)° and 12.07 (11)° with the chloro-substituted phenyl ring and the chromene ring, respectively. The mol-ecular structure features a short C-H⋯O contact, which generates an S(6) ring motif. The crystal structure is stabilized by inter-molecular N-H⋯O hydrogen bonds, which link the mol-ecules into chains along the b axis. π-π stacking inter-actions [centroid-centroid distance = 3.4813 (15) Å] are also present.

(E)-6-Bromo-3-{2-[2-(2-chloro-benzyl-idene)hydrazin-yl]thia-zol-5-yl}-2H-chromen-2-one dimethyl sulfoxide monosolvate.

In the title compound C(19)H(11)N(3)O(2)SClBr·C(2)H(6)OS, the mol-ecule adopts an E configuration about the central C=N double bond. The chromene ring system and the thia-zole ring are approximately planar, with maximum deviations of 0.027 (2) and 0.003 (1) Å, respectively. The central thia-zole ring makes dihedral angles of 21.82 (9) and 5.88 (7)° with the chloro-substituted phenyl ring and the chromene ring, respectively. In the crystal, mol-ecules are connected via N-H⋯O, N-H⋯S and C-H⋯O hydrogen bonds, forming supra-molecular chains along the c axis. An intra-molecular C-H⋯O hydrogen bond occurs. π-π inter-actions are observed between the thia-zole and phenyl rings [centroid-centroid distance = 3.6293 (10) Å]. A short Br⋯Cl contact of 3.37 (6) Šalso occurs.

(E)-3-(2-{2-[1-(3-Hy-droxy-phen-yl)ethyl-idene]hydrazin-yl}-1,3-thia-zol-4-yl)-2H-chromen-2-one.

In the title compound, C(20)H(15)N(3)O(3)S, the thia-zole ring is approximately planar, with a maximum deviation of 0.003 (1) Å, and makes dihedral angles of 7.44 (6) and 1.88 (6)° with the hy-droxy-substituted phenyl ring and the pyran ring, respectively. The hydroxyl group is disordered over two sets of sites, with an occupancy ratio of 0.567 (3):0.433 (3). In the crystal, the major disorder component mol-ecules are connected via bifurcated (three-centre) O-H⋯O and C-H⋯O hydrogen bonds, generating R(1) (2)(6) motifs and resulting in supra-molecular chains along the a axis. In the minor occupancy component, however, mol-ecules are connected via C-H⋯O hydrogen bonds, forming supra-molecular chains along the b axis. Furthermore, the crystal structure is stabilized by π-π inter-actions between the thia-zole rings [centroid-centroid distance = 3.5476 (7) Å].

6-Bromo-3-{2-[2-(diphenyl-methyl-ene)hydrazin-yl]-1,3-thia-zol-5-yl}-2H-chromen-2-one chloro-form monosolvate.

In the title compound, C(25)H(16)BrN(3)O(2)S·CHCl(3), the thia-zole ring is approximately planar [maximum deviation = 0.002 (3) Å] and makes dihedral angles of 10.75 (14) and 87.75 (15)/2.80 (14)° with the pyran ring system and the two terminal phenyl rings, respectively. The solvent mol-ecule is disordered over two sets of sites, with refined occupancies of 0.639 (7) and 0.361 (7). In the crystal, mol-ecules are connected via pairs of weak C-H⋯O inter-actions, forming centrosymmetric dimers. An intra-molecular C-H⋯O hydrogen bond generates an S(6) ring motif.

Synthesis and antimicrobial properties of some new thiazolyl coumarin derivatives.

Two novel series of hydrazinyl thiazolyl coumarin derivatives have been synthesized and fully characterized by IR, (1)H NMR, (13)C NMR, elemental analysis and mass spectral data. The structures of some compounds were further confirmed by X-ray crystallography. All of these derivatives, 10a-d and 15a-h, were screened in vitro for antimicrobial activity against various bacteria species including Mycobacterium tuberculosis and Candida albicans. The compounds 10c, 10d and 15e exhibited very good activities against all of the tested microbial strains.

3-{2-[2-(2-Fluoro-benzyl-idene)hydrazin-yl]-1,3-thia-zol-4-yl}-2H-chromen-2-one.

In the title compound, C(19)H(12)FN(3)O(2)S, the chromene ring system and the thia-zole ring are approximately planar [maximum deviations of 0.023 (3) Šand 0.004 (2) Å, respectively]. The chromene ring system is inclined at angles of 4.78 (10) and 26.51 (10)° with respect to the thia-zole and benzene rings, respectively, while the thia-zole ring makes a dihedral angle of 23.07 (12)° with the benzene ring. The mol-ecular structure is stabilized by an intra-molecular C-H⋯O hydrogen bond, which generates an S(6) ring motif. The crystal packing is consolidated by inter-molecular N-H⋯O hydrogen bonds, which link the mol-ecules into chains parallel to [100], and by C-H⋯π and π-π [centroid-centroid distance = 3.4954 (15) Å] stacking inter-actions.

(Z)-3-(2-{2-[1-(4-Hy-droxy-phen-yl)ethyl-idene]hydrazin-1-yl}-1,3-thia-zol-4-yl)-2H-chromen-2-one.

In the title compound, C(20)H(15)N(3)O(3)S, an intra-molecular C-H⋯O hydrogen bond generates an S(6) ring motif. The chromene ring system is inclined at dihedral angles of 14.21 (9) and 9.91 (10)°, respectively, with respect to the thia-zole and benzene rings. The thia-zole ring makes a dihedral angle of 24.06 (11)° with the benzene ring. In the crystal structure, O-H⋯O hydrogen bonds link the mol-ecules into a zigzag chain along [20]. Weak N-H⋯O and C-H⋯O inter-actions connect the chains into a three-dimensional network. π-π stacking inter-actions with a centroid-centroid distance of 3.4209 (14) Šare also observed between the chains.