Yibing Wu

Design, synthesis and biological activity of pyrazolo(1,5-a)pyrimidin-7(4H)-ones as novel Kv7/KCNQ potassium channel activators

Voltage-gated Kv7/KCNQ/M-potassium channels play a pivotal role in controlling neuronal excitability. Genetic reduction of KCNQ channel activity as a result of mutations causes various human diseases such as epilepsy and arrhythmia. Therefore, discovery of small molecules that activate KCNQ channels is an important strategy for clinical intervention of membrane excitability related disorders. In this study, a series of pyrazolo[1,5-a]pyrimidin-7(4H)-ones (PPOs) have been found to be novel activators (openers) of KCNQ2/3 potassium channels through high-throughput screening by using atomic absorption rubidium efflux assay. Based on structure-activity relationship (SAR), the substituted PPOs have been optimized. The 5-(2,6-dichloro-5-fluoropyridin-3-yl)-3-phenyl-2-(trifluoromethyl) pyrazolo[1,5-a]pyrimidin-7(4H)-one (17) was identified as a novel, potent, and selective KCNQ2/3 potassium channel opener by patch-clamp recording assay.

Differentiation of genuine Inula britannica L. and substitute specimens based on the determination of 15 components using LC-MS/MS and principal components analysis.

The aim of this study was to investigate the chemical differences between genuine Inula britannica L. (I. britannica) and substitute specimens. A linear ion trap LC-MS/MS analytical method has been developed for the identification and quantification of 15 major components from I. britannica. Data acquisition was performed in multiple-reaction-monitoring transitions mode followed by an information-dependent acquisition using the enhanced product ion (EPI) scan in one run. The target compounds were further identified and confirmed using an EPI spectral library. The determination results of 45 batches of samples were then analysed and classified by principal component analysis (PCA). The content of 11 components could be used to distinguish the two official Flos Inulae species (I. britannica and Inula japonica) from unofficial species (Inula hupehensis), and the content of 3 components could be used to differentiate the two official species.

Polyhydroxytriterpenoids and Phenolic Constituents from Forsythia suspensa (Thunb.) Vahl Leaves

Forsythia suspensa (Thunb.) Vahl leaves have been consumed in China as a health-promoting functional tea for centuries. Three new polyhydroxytriterpenoid glycosides named suspensanosides A-C (1-3), seven known polyhydroxytriterpenoids (4-10), and 12 known phenolics (11-22) were identified from F. suspensa leaves. Compounds 1-10, 15-17, and 22 have not been found in the Forsythia genus previously, whereas compound 14 was first reported to be isolated from the leaves of F. suspensa. All isolates were tested for their antiproliferative activities on BGC-823 and MCF-7 human tumor cell lines, whereas all phenolics were further investigated for their antioxidant activities by a DPPH assay. The results clearly demonstrate that triterpenoids, especially ursane-type triterpenoids, and the diverse phenolic components are crucial for the beneficial effects of F. suspensa leaves.

A chemometric-assisted LC–MS/MS method for the simultaneous determination of 17 limonoids from different parts of Xylocarpus granatum fruit

The marine mangrove Xylocarpus granatum is used as a folk medicine and is rich in bioactive limonoids. The quantitative determination of the chemical composition and distribution of limonoids in different parts of X. granatum fruit (fruit peel, seed coat, seed kernels, seed, and fruit) is significant for authentication and quality control purposes. However, the quantitative determination of limonoids in X. granatum has not yet been reported. In this study, a chemometric-assisted liquid chromatography–tandem mass spectrometry (LC–MS/MS) method was developed and validated for the simultaneous determination of 17 limonoids to reveal the chemical composition and distribution in different parts of X. granatum fruit. Ultrasonic-assisted extraction, optimized by response surface methodology (RSM), was more accurate than the general one-variable-at-a-time method. The overall distribution of 17 limonoids in different parts of X. granatum fruit had the following order: seed kernels > seed > fruit, and 13 limonoids showed a rank order of seed kernels > seed > fruit > fruit peel > seed coat. Furthermore, principal component analysis (PCA) and orthogonal partial least squares discriminant analysis (OPLS-DA) were used to analyze the LC–MS/MS data and provide a chemometric model for easy visualization and interpretation to classify the different parts of X. granatum fruit. In addition, the study indicated that the chemometric-assisted strategy, consisting of RSM, PCA, and OPLS-DA for the development, optimization, and data analysis of multicomponent quantitation by LC–MS/MS, is effective and feasible. This study provided the chemical composition and distribution evidence for the authentication and quality control of X. granatum fruit.

A New Limonoid from Xylocarpus granatum

A new limonoid, named xylocartin C (1), was isolated from the seeds of Xylocarpus granatum and its structure was elucidated on the basis of one- and two-dimensional NMR (including 1H, 13C NMR, DEPT, 1H–1H COSY, HSQC, HMBC, and NOESY).

Chemical Constituents of Xylocarpus granatum

Xylocarpus granatum K. D. Koenig, a marine mangrove plant distributed mainly along the seashore along the Indian Ocean and in Southeast Asia, is used in folk medicine in Southeast Asia for the treatment of diarrhea, cholera, and fever diseases such as malaria, and also as an antifeedant [1, 2]. Since the first limonoid, gedunin, was reported from this plant [3], the unique structural patterns of limonoids have attracted considerable attention from medicinal chemists as well as chemical biologists because of their fascinating structural diversity and important biological activities. As a result, more than 50 limonoid derivatives have been isolated from X. granatum, and they have been classified into phragmalin, mexicanolide, obacunol, and andirobin types [4–9]. In our effort to study the biological activity of natural products used as the lead molecule of drugs from Chinese medicinal plants, nine limonoid compounds and two steroids were isolated from a dichloromethane extract of the seed of Xylocarpus granatum. We report herein the isolation and structural elucidation of all these compounds. From a dichloromethane extract of the seed of X. granatum, xylomexicanin A (1) [10], xylogranatin D (2) [7], hainangranatumin A (3) [11], xylogranatin C (4) [7], hainangranatumin C (5) [11], xylocarpin H (6) [9], xyloccensin K (7) [12], piscidinol G (8) [13], xylocarpin G (9) [9], hydroxydammarenone-II (10), and stigmasterol (11) were isolated and purified by repeated chromatography over a silica gel column. The structure of every compound was postulated on the basis of spectroscopic analysis. Hydroxydammarenone-II (10) from this genus is reported for the first time here.

A monoterpene and two sesquiterpenoids from the flowers of Achillea millefolium

A monoterpene and a pair of epi-isomers of norsesquiterpenoids were isolated from the flowers of Achillea millefolium, and their structures were established as 1-hydroxy-2R,3R-isopyliden-hex-5-en-4-one (1), isololiolide (2), and 6-epiloliolide (3) on the basis of spectral analysis.

Antitumor Activities of Six Quassinoids from Ailanthus altissima

Six known quassinoids were isolated from the bark of Ailanthus altissima. Their structures were elucidated by spectroscopic methods. Compounds 1–6 were screened for their antitumor activities evaluated by MTT assay.

New Thiophene Acetylene from Echinops spinosissimus subsp. spinosus

A new thiophene acetylene, named 2,2-dimethyl-4-[5′-(prop-1-ynyl)-2,2′-bithiophen-5-yl]-1,3-dioxolane (1), was isolated from the roots of Echinops spinosus, and the structure was elucidated on the basis of oneand two-dimensional NMR (including 1H, 13C NMR, DEPT, 1H–1H COSY, HSQC, and HMBC).

Granaxylocartin A, New Limonoid from the Seeds of Xylocarpus granatum

A new limonoid, named granaxylocartin A (1), was isolated from the seeds of Xylocarpus granatum, and the structure was elucidated on the basis of one- and two-dimensional NMR (including 1H, 13C NMR, DEPT, 1H–1H COSY, HSQC, HMBC, and NOESY).