ABSTRACT
Taiwania cryptomerioides Hayata is an endangered relict plant belonging to Taxodiaceae, and it is also an endemic plant to China. The decay-resistant of Taiwania timber can provide highly quality wood for building and furniture. Plenty of regenerative of leaves of T.â cryptomerioides also has been used as a resource for the discovery of new dimeric diterpenoids. In a search for structurally diverse dimeric diterpenoids and potent bioactive isolates, ten new heterodimeric diterpenoids, taiwaniadducts K-T (1-4, 6, 8-11, and 14), along with five known ones (5, 7, 12, 13, and 15), were isolated from the leaves of T.â cryptomerioides. These new compounds were defined by comprehensive spectroscopic analyses, putative biosynthetic pathways, and the values of optical. Biologically, anti-multidrug resistance (MDR) activities of compounds were evaluated. Compounds 4 and 10 exerted a 9.18-fold potentiation effect on bortezmib (BTZ) susceptibility at a tested concentration (20â µM) better than the positive control verapamil. The research of the leaves of T.â cryptomerioides not only added the new data to the structural diversity and activities of dimeric diterpenoids but also could provide support for the medical and industrial application of the leaves of this endangered relict plant.
Subject(s)
Cupressaceae , Diterpenes , Diterpenes/chemistry , Plant Extracts/chemistry , Wood , Spectrum Analysis , Cupressaceae/chemistry , Molecular StructureABSTRACT
Taxodisones A and B, C30-terpenes with an unprecedented tetracyclo[12.4.0.0.2,709,14]octodecane core, were isolated from the seeds of Taxodium distichum. Their structures, including their configurations, were unambiguously determined. Their biomimetic synthesis suggests that they stem from diterpenes and monoterpenes, and not from squalene or oxidosqualene. In addition, their bioactivities were also evaluated.
Subject(s)
Diterpenes/chemistry , Taxodium/chemistry , Biomimetics , Catalysis , Coordination Complexes/chemistry , Crystallography, X-Ray , Cycloaddition Reaction , Diterpenes/metabolism , Erbium/chemistry , Molecular Conformation , Seeds/chemistry , Seeds/metabolism , Taxodium/metabolism , Terpenes/chemistry , Terpenes/metabolismABSTRACT
Two uncommon C37 heterodimeric diterpenoids, taicrypnacids A (1) and B (2), and a known labdane-type diterpenoid (3) were isolated from the leaves of Taiwania cryptomerioides. Several techniques, such as comprehensive spectroscopic analysis, chemical conversion, X-ray crystallography, and ECD data, were employed to define the structures. The two new compounds displayed cytotoxicity against human breast cancer (MCF-7), osteosarcoma (U-2 OS), and human colon carcinoma (HCT-116) cell lines, while the methyl ester 1a showed no activity. Compound 1 induced Ca2+-ROS pathway-mediated endoplasmic reticulum stress, and excessive stress led to cell death by activating apoptosis and autophagy.
Subject(s)
Cupressaceae/chemistry , Diterpenes/isolation & purification , Antineoplastic Agents, Phytogenic/pharmacology , Dimerization , Diterpenes/chemistry , Drug Screening Assays, Antitumor , HCT116 Cells , Humans , MCF-7 Cells , Molecular Structure , Spectrum Analysis/methods , StereoisomerismABSTRACT
Biogenesis-inspired chemical research of the leaves of Taiwania cryptomerioides afforded four unprecedented dimeric diterpenes, featuring a tetracyclic [7. 75, 9. 4. 05, 10. 08, 9] octodecane core: taiwanoids A-D (1-4). The structures of these compounds were determined on the basis of comprehensive spectral analysis, chemical conversions and X-ray crystallography. A possible biosynthetic pathway for compounds 1-4 was proposed. Compounds 2 and 3 exerted a 5.37 and 6.26-fold potentiation effect on bortezmib (BTZ) susceptibility at a tested concentration of 20 µM, respectively.
Subject(s)
Abietanes/chemistry , Cupressaceae/chemistry , Abietanes/pharmacology , Antineoplastic Agents/pharmacology , Bortezomib/pharmacology , Cell Line, Tumor , Crystallography, X-Ray , Dimerization , Drug Resistance, Neoplasm/drug effects , Humans , Models, Molecular , Neoplasms/drug therapy , Plant Extracts/chemistry , Plant Extracts/pharmacologyABSTRACT
Artemisians A-D (1-4), the first examples of [4 + 2] Diels-Alder type adducts presumably biosynthesized from a rare 1, 10-4, 5-diseco-guaianolide and a guaianolide diene, along with their possible precursor 5, were isolated from the traditional Chinese medicine Artemisia argyi. The structures of 1-4 were elucidated by extensive spectroscopic analyses and calculated electronic circular dichroism. Compound 2, with an IC50 value of 3.21 µM, exhibited significant antiproliferative activity via apoptosis induction and G2/M arrest in MDA-MB-468 cells.
ABSTRACT
ETHNOPHARMACOLOGICAL RELEVANCE: The Gnaphalium affine D. Don is used in China as a folk medicine to treat gout, anti-inflammatory, antitussive and expectorant activities. The aim of this study was to evaluate the potential of the extract of G. affine to treat hyperuricemia and acute gouty arthritis in animal model. MATERIALS AND METHODS: G. affine extract was evaluated in an experimental model with potassium oxonate (PO) induced hyperuricemia in mice which was used to evaluate anti-hyperuricemia activity and xanthine oxidase (XO) inhibition. Therapies for acute gouty arthritis was also investigated on monosodium urate (MSU) crystal induced paw edema model. RESULTS: G. affine extract showed expressive results on active in reducing serum uric acid (Sur) through effect renal mGLUT9 and mURAT1 mainly and inhibit XO activity in vivo. The extract of G. affine also showed significant anti-inflammatory activity and reduced the paw swelling on MSU crystal-induced paw edema model. Meanwhile, eight major compounds were identified by HPLC-ESI-QTOF-MS/MS. CONCLUSIONS: The extract of G. affine showed significant effect on evaluated models and therefore may be active agents for the treatment of hyperuricemia and acute gouty arthritis.
Subject(s)
Arthritis, Gouty/drug therapy , Gnaphalium/chemistry , Hyperuricemia/drug therapy , Plant Extracts/pharmacology , Animals , Anti-Inflammatory Agents/isolation & purification , Anti-Inflammatory Agents/pharmacology , Chromatography, High Pressure Liquid , Disease Models, Animal , Edema/drug therapy , Male , Mice , Mice, Inbred ICR , Oxonic Acid/toxicity , Tandem Mass Spectrometry , Uric Acid/blood , Xanthine Oxidase/antagonists & inhibitorsABSTRACT
Ten new (1-10) and seventeen known (11-27) neo-clerodane diterpenoids substituted with nicotinoyloxyl were isolated from the plant Scutellaria barbata and their structures were established by extensive spectroscopic analysis. Chemoreversal effects of these neo-clerodane diterpenoids on multidrug resistance were evaluated in breast cancer multidrug-resistant MCF-7/ADR cells that overexpress P-glycoprotein. Four compounds (11, 14, 16, and 18) exhibited better chemoreversal abilities than the classical P-gp inhibitor verapamil and the most potent compound 11 reduced IC50 value of adriamycin in MCF-7/ADR cells from 58.8 µM to 1.3 µM. Mechanistic investigations showed that compound 11 reversed multidrug resistance through suppressing the activity of P-gp and restraining the expression of P-glycoprotein. In the present study, the structure-activity relationships of neo-clerodane diterpenoids were also discussed.
