[Show abstract][Hide abstract] ABSTRACT: Herein, we evaluated the anti-cancer effect and molecular mechanisms of a novel betulinic acid (BA) derivative, SYK023, by using two mouse models of lung cancer driven by KrasG12D or EGFRL858R. We found that SYK023 inhibits lung tumor proliferation, without side effects in vivo or cytotoxicity in primary lung cells in vitro. SYK023 triggered endoplasmic reticulum (ER) stress. Blockage of ER stress in SYK023-treated cells inhibited SYK023-induced apoptosis. In addition, we found that the expression of cell cycle-related genes, including cyclin A2, B1, D3, CDC25a, and CDC25b decreased but, while those of p15INK4b, p16INK4a, and p21CIP1 increased following SYK023 treatment. Finally, low doses of SYK023 significantly decreased lung cancer metastasis in vitro and in vivo. Expression of several genes related to cell migration, including synaptopodin, were downregulated by SYK023, thereby impairing F-actin polymerization and metastasis. Therefore, SYK023 may be a potentially therapeutic treatment for metastatic lung cancer.
[Show abstract][Hide abstract] ABSTRACT: Six new prenylated benzophenones, (-)-nemorosonol (1) and trijapins A-E (2-6), were isolated from the aerial parts of Triadenum japonicum. (-)-Nemorosonol (1) and trijapins A-C (2-4) have a common tricyclo[188.8.131.52(3,7)]decane skeleton, while 1 is an enantiomer of (+)-nemorosonol previously isolated from Clusia nemorosa. The absolute configuration of (-)-nemorosonol (1) was assigned by ECD spectroscopy. Trijapins A-C (2-4) are analogues of 1 possessing an additional tetrahydrofuran ring. Trijapins D (5) and E (6) are prenylated benzophenones with a 1,2-dioxane moiety and a hydroperoxy group, respectively. (-)-Nemorosonol (1) exhibited antimicrobial activity against Escherichia coli (MIC, 8 μg/mL), Staphylococcus aureus (MIC, 16 μg/mL), Bacillus subtilis (MIC, 16 μg/mL), Micrococcus luteus (MIC, 32 μg/mL), Aspergillus niger (IC50, 16 μg/mL), Trichophyton mentagrophytes (IC50, 8 μg/mL), and Candida albicans (IC50, 32 μg/mL), while trijapin D (5) showed antimicrobial activity against C. albicans (IC50, 8 μg/mL).
No preview · Article · Jan 2015 · Journal of Natural Products
[Show abstract][Hide abstract] ABSTRACT: Four new lindenane sesquiterpenoid dimers, spicachlorantins G-J (1-4), were isolated from the roots of Chloranthus spicatus together with seven known compounds, including chloramultilide A, shizukaol B, shizukaol D, shizukaol F, shizukaol P, chlorahololide D, and cycloshizukaol A. The planar structures of the new compounds were established by 1D-, 2D-NMR, and MS analyses. The absolute configurations of these compounds were determined by analyzing rotating Overhauser enhancement and exchange spectroscopy (ROESY) and circular dichroism (CD) spectra.
No preview · Article · Mar 2012 · Chemical & pharmaceutical bulletin
[Show abstract][Hide abstract] ABSTRACT: In this study, 22 new betulinic acid (BA) derivatives were synthesized and tested for their inhibition of the chymotrypsin-like activity of 20S proteasome. From the SAR study, we concluded that the C-3 and C-30 positions are the pharmacophores for increasing the proteasome inhibition effects, and larger lipophilic or aromatic side chains are favored at these positions. Among the BA derivatives tested, compounds 13, 20, and 21 showed the best proteasome inhibition activity with IC(50) values of 1.42, 1.56, and 1.80 μM, respectively, which are three to fourfold more potent than the proteasome inhibition controls LLM-F and lactacystin.
[Show abstract][Hide abstract] ABSTRACT: Two new caffeoyl quinic acid α-glucosides, together with three known caffeoyl quinic acids and five known flavonoid glucosides, were isolated from the leaves of Moringa oleifera Lam. The structures of the new compounds were elucidated as 4-O-(4'-O-α-D-glucopyranosyl)-caffeoyl quinic acid (1) and 4-O-(3'-O-α-D-glucopyranosyl)-caffeoyl quinic acid (2) by spectroscopic analyses.
No preview · Article · Jul 2011 · Journal of Natural Medicines
[Show abstract][Hide abstract] ABSTRACT: ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
[Show abstract][Hide abstract] ABSTRACT: Spicachlorantins C–F (1–4), new lindenane–sesquiterpene dimers possessing a hydroperoxy group, were isolated from the roots of Chloranthus spicatus. Their structures, including the absolute stereostructures, were established by 1D and 2D NMR, as well as CD spectroscopic analyses. Spicachlorantins C–F were considered to be biogenetic precursors for the corresponding hydroxy derivatives of dimeric lindenane sesquiterpenes distributed in Chloranthus plants.
Full-text · Article · Nov 2009 · Tetrahedron Letters
[Show abstract][Hide abstract] ABSTRACT: A xanthonolignoid, 2-O-demethylkielcorin, and a phenylxanthone, chinexanthone A, were isolated from stems of Hypericum chinense together with four known xanthonolignoids and seven known xanthones. Their structures were established by spectroscopic analysis, as their optical properties and absolute stereochemistry determined. The cytotoxicities of the isolated xanthone derivatives as well as additional 32 xanthones against a panel of human cancer cell lines were also evaluated.
[Show abstract][Hide abstract] ABSTRACT: Two new lindenane sesquiterpene dimers, spicachlorantins A and B (1 and 2), were isolated from the roots of Chloranthus spicatus along with a known related compound, chloramultilide A (3). Their structures and the absolute stereostructures were established by 1D and 2D NMR as well as by CD spectroscopic analyses.
No preview · Article · Aug 2009 · Phytochemistry Letters