No abstract

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.

BackgroundCoumarin 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 propertiesResultsMicrowave 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 assaysConclusionsMicrowave 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.

Quassinoids, the major secondary metabolites of roots, improve male fertility. Hence, it is crucial to investigate their quantitative level in 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 roots from different regions was investigated. TheH-NMR spectra of the quassinoids, eurycomanone, eurycomanol, 13,21-dihydroeurycomanone, and eurycomanol-2---D-glycopyranoside were obtained. The H-NMR profiles of 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 T 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, -glucose, eurycomanone, eurycomanol, 13,21-dihydroeurycomanone, and eurycomanol-2---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---D-glycopyranoside) ppm. The Hotelling's T plot revealed no outlier. The orthogonal partial least-squares discriminant analysis model showed that choline, eurycomanol, eurycomanol-2---D-glycopyranoside, and lactic and succinic acid levels were different among regions. Terengganu and Perak samples contained higher amounts of eurycomanol and eurycomanol-2---D-glycopyranoside, respectively. The current approach efficiently detected root metabolites, quantified the quassinoids, and discriminated roots from different locations. These findings could be applicable to future research on where the higher content of quassinoids is required.

No abstract