ABSTRACT
The chemical composition of V. pyrantha resin (VpR) and fractions (VpFr1-7 and VpWS) were assessed by LC-MS and NMR. Twenty-eight metabolites were identified, including 16 diterpenoids, seven nor-diterpenoids, one fatty acid, one bis-diterpenoid, one steroid, one flavonoid, and one triterpenoid. The pharmacological potential of VpR, VpFr1-7, and isolated compounds was assessed by determining their antioxidant, antimicrobial, and cytotoxic activities. VpFr4 (IC50 = 205.48 ± 3.37 µg.mL-1) had the highest antioxidant activity, whereas VpFr6 (IC50 = 842.79 ± 10.23 µg.mL-1) had the lowest. The resin was only active against Staphylococcus aureus (MIC 62.5 µg.mL-1) and Salmonella choleraesius (MIC and MFC 500 µg.mL-1), but fractions were enriched with antibacterial compounds. V. pyrantha resin and fractions showed great cytotoxic activity against HCT116 (IC50 = 20.08 µg.mL-1), HepG2 (IC50 = 20.50 µg.mL-1), and B16-F10 (12.17 µg.mL-1) cell lines. Multivariate statistical analysis was used as a powerful tool to pinpoint possible metabolites responsible for the observed activities.
Subject(s)
Anti-Infective Agents , Antineoplastic Agents , Diterpenes , Plant Extracts/chemistry , Molecular Structure , Anti-Infective Agents/pharmacology , Anti-Bacterial Agents/pharmacology , Antioxidants/pharmacology , Antioxidants/chemistry , Diterpenes/pharmacologyABSTRACT
A bioactivity-guided isolation from the aerial parts of Phyllanthus rheophyticus obtained 17 undescribed ent-cleistanthane-type diterpenoids, namely phyllarheophols A-Q, as well as 12 known analogs. Their structures were characterized by a combination of spectroscopic data interpretation, single-crystal X-ray diffraction and ECD analysis. The anti-inflammatory activities of these compounds were evaluated by measuring their inhibitory effects on NO production in LPS-stimulated RAW264.7 macrophages, and their preliminary structure-activity relationships were also discussed. Further study showed that promising compounds phyllarheophol D and phyacioid B significantly suppressed the expressions of cytokines and nitric oxide synthase through the NF-κB signaling pathway.
Subject(s)
Anti-Inflammatory Agents , Diterpenes , Phyllanthus , Anti-Inflammatory Agents/chemistry , Anti-Inflammatory Agents/isolation & purification , Anti-Inflammatory Agents/pharmacology , Diterpenes/chemistry , Diterpenes/isolation & purification , Diterpenes/pharmacology , Lipopolysaccharides , Macrophages/drug effects , Macrophages/enzymology , Macrophages/immunology , Macrophages/metabolism , Molecular Structure , Nitric Oxide/antagonists & inhibitors , Phyllanthus/chemistry , Structure-Activity Relationship , NF-kappa B/metabolism , Plant Components, Aerial/chemistry , Tumor Necrosis Factor-alpha/immunology , Tumor Necrosis Factor-alpha/metabolism , Interleukin-6/immunology , Interleukin-6/metabolism , Nitric Oxide Synthase Type II/metabolism , RAW 264.7 Cells , Animals , MiceABSTRACT
Five undescribed diterpenoids, including two ent-cleistanthane-type diterpenoids aconicleistanthanes A and B, a hetisine-type diterpenoid aconihetisine A, two aconitines-type diterpenoids aconicarmines A and B, and thirteen known diterpenoids alkaloids, were co-isolated from the lateral root of the Aconitum carmichaelii Debeaux (Ranunculaceae). Their structures were elucidated based on spectroscopic methods, and the absolute configurations were determined by X-ray diffraction and electronic circular dichroism (ECD) calculations. Among them, aconicleistanthanes A and B as ent-cleistanthane-type diterpenoid featuring a unique five-membered lactone D ring, is the first reported example of ent-cleistanthane-type diterpenoids in the Aconitum, which provided a new type of diterpene metabolites for Aconitum and enriched the chemical space of the plant of the Aconitum. In the bioassays, aconicleistanthane A significantly suppressed the production of pro-inflammatory mediators (IL-6, IL-1ß and COX-2) and the protein expression of the enzyme iNOS at the concentration of 6.25 µM.
ABSTRACT
Six diterpenoids including three ent-kauranes (1-2, 4) and three cleistanthanes (3, 5-6) were isolated from the roots and stems of Phyllanthus acidus (L.) Skeels. Of them, (16S)-ent-16,17,18-tri-hydroxy-19-nor-kaur-4-en-3-one (1), phyllanthone A (2), and 6-hydroxycleistanthol (3) are new compounds, while the ent-kaurane diterpenoids were reported from the titled plant for the first time. Their structures were elucidated on the basis of the extensive spectroscopic analyses. Compounds 2 and 4-6 displayed cytotoxic potential with IC50 values ranging from 1.96 to 29.15 µM. They also showed moderate anti-inflammatory activities (IC50 = 6.30-12.05 µM). Particularly, the new ent-kaurane 2 displayed cytotoxic potential against HL-60 (IC50 = 2.00 µM) and MCF-7 (IC50 = 3.55 µM) cells, and anti-inflammatory activity (IC50 = 6.47 µM).
Subject(s)
Diterpenes, Kaurane/toxicity , Diterpenes/toxicity , Phyllanthus/chemistry , Plant Extracts/toxicity , Alkaloids/chemistry , Alkaloids/isolation & purification , Alkaloids/toxicity , Cell Line, Tumor , Diterpenes/chemistry , Diterpenes, Kaurane/chemistry , Humans , Inhibitory Concentration 50 , Magnetic Resonance Spectroscopy , Molecular Structure , Plant Extracts/chemical synthesis , Plant Roots/chemistry , Plant Stems/chemistryABSTRACT
Phyllaciduloids E (1) and F (2), two new cleistanthane diterpenoids, were isolated from the leaves of Phyllanthus acidus (L.) Skeels (Phyllanthaceae). Their planar structures were established by spectroscopic analysis and comparison with literature values. The relative configurations of phyllaciduloids E and F were confirmed by DFT-NMR chemical shift calculations and subsequent CP3 probability methods. Phyllaciduloids E and F were evaluated for their cytotoxicity. However, no significant activities were detected at concentrations up to 40 µM.[Formula: see text].
Subject(s)
Diterpenes , Phyllanthus , Diterpenes/analysis , Diterpenes/pharmacology , Molecular Structure , Phyllanthus/chemistry , Plant Extracts/analysis , Plant Leaves/chemistryABSTRACT
Phytochemical investigation on the nonpolar extracts of P. acidus leaves afforded three new cleistanthane diterpenoids, named phyllanacidins A-C (1-3), in addition to three known ones (4-6). Among them, compounds 2 and 3 represent the first examples of 17-nor cleistanthane diterpenoids. Their structures including absolute configurations were elucidated on the basis of extensive spectroscopic data and single crystal X-ray diffraction analysis. All the isolated cleistanthane diterpenoids were evaluated for their cytotoxic activities against five human cancer cell lines. Compounds 4-6 exhibited moderate cytotoxicity with IC50 values ranging from 16.11 to 30.82 µM.
Subject(s)
Antineoplastic Agents, Phytogenic/pharmacology , Diterpenes/pharmacology , Phyllanthus/chemistry , Antineoplastic Agents, Phytogenic/isolation & purification , Cell Line, Tumor , China , Diterpenes/isolation & purification , Drug Screening Assays, Antitumor , Humans , Molecular Structure , Phytochemicals/isolation & purification , Phytochemicals/pharmacology , Plant Leaves/chemistryABSTRACT
Studies on the relationship of nitric oxide (NO) and inflammation have revealed that compounds with NO inhibitory effects are potentially useful for inflammation and related inflammatory disorders. A phytochemical investigation to obtain new NO inhibitors resulted in the isolation of two new cleistanthane diterpenoids (1 and 2) and 11 known terpenoids (3-13) from Trigonostemon heterophyllus. The structures of these terpenoids were established by analysis of their NMR, MS, and electronic circular dichroism (ECD) data. Compounds 1 and 2 possess rare 3,4-seco-cleistanthane diterpenoid skeletons. All of the isolates were evaluated biologically for their NO inhibitory effects in lipopolysaccharide (LPS)-induced murine microglial BV-2 cells and compounds 1, 6, and 8-10 showed strong NO inhibitory effects with IC50 values less than 40⯵M. Using Western blotting experiments and molecular docking, the possible mechanism of NO inhibition was investigated.
Subject(s)
Anti-Inflammatory Agents/pharmacology , Drugs, Chinese Herbal/pharmacology , Euphorbiaceae/chemistry , Nitric Oxide/antagonists & inhibitors , Phytochemicals/pharmacology , Plant Stems/chemistry , Animals , Anti-Inflammatory Agents/chemistry , Anti-Inflammatory Agents/isolation & purification , Cell Line , Dose-Response Relationship, Drug , Drugs, Chinese Herbal/chemistry , Drugs, Chinese Herbal/isolation & purification , Lipopolysaccharides/antagonists & inhibitors , Lipopolysaccharides/pharmacology , Mice , Molecular Docking Simulation , Molecular Structure , Nitric Oxide/biosynthesis , Phytochemicals/chemistry , Phytochemicals/isolation & purification , Structure-Activity RelationshipABSTRACT
Three new cleistanthane diterpenoids, phyllanglins A-C (1-3), a new natural product, 4-acetyl-bergenin (4), and three known compounds (5-7) were isolated from the roots of Phyllanthus glaucus. Their structures were elucidated by extensive spectroscopic data analyses and single-crystal X-ray diffraction. Phyllanglins A-C were unusual cleistanthane diterpenoids with phenylacetylene moieties, and a plausible biogenetic pathway was proposed to discuss the origins of them. All of the isolates were evaluated for their anti-inflammatory activities.
Subject(s)
Acetylene/analogs & derivatives , Diterpenes/isolation & purification , Phyllanthus/chemistry , Plant Roots/chemistry , Acetylene/isolation & purification , Animals , Anti-Inflammatory Agents/isolation & purification , Anti-Inflammatory Agents/pharmacology , Crystallography, X-Ray , Diterpenes/pharmacology , Mice , Molecular Structure , RAW 264.7 CellsABSTRACT
Four new cleistanthane diterpenoids, phyllaciduloids A-D (1-4), were isolated from the roots and stems of Phyllanthus acidus (L.) Skeels (Phyllanthaceae). Their structures were elucidated on the basis of extensive spectroscopic analysis. Phyllaciduloids B-D (2-4) present in their structures with ether bond between C-7 and C-16, which were rarely reported. All the isolates were evaluated for their cytotoxic activities against five human cancer cell lines.
Subject(s)
Diterpenes/isolation & purification , Phyllanthus/chemistry , Antineoplastic Agents, Phytogenic , Cell Line, Tumor , Humans , Molecular Structure , Plant Roots/chemistry , Plant Stems/chemistryABSTRACT
A phytochemical investigation to obtain new NO inhibitors led to the isolation of nine compounds including one new guaiane-type sesquiterpenoid (1) and two new cleistanthane diterpenoids (2 and 3) from the stems of Trigonostemon howii. Their structures were elucidated on the basis of extensive 1D and 2D NMR spectroscopic data analysis, and the absolute configurations of new compounds 1-3 were established via comparison of experimental and calculated electronic circular dichroism (ECD) spectra. Compounds 2 and 3 possess a rare 3,4-seco-cleistanthane diterpenoid skeleton. All of the compounds showed inhibitory effects on lipopolysaccharide-induced NO production in murine microglial BV-2 cells. The further molecular docking studies indicated the strong interactions between some bioactive compounds with the iNOS protein, which revealed the possible and potential mechanism of NO inhibition of bioactive compounds.
Subject(s)
Diterpenes/isolation & purification , Diterpenes/pharmacology , Enzyme Inhibitors/chemistry , Euphorbiaceae/chemistry , Nitric Oxide Synthase Type II/antagonists & inhibitors , Phytochemicals/chemistry , Sesquiterpenes, Guaiane/isolation & purification , Sesquiterpenes, Guaiane/pharmacology , Binding Sites , Catalytic Domain , Circular Dichroism , Diterpenes/chemistry , Enzyme Inhibitors/metabolism , Euphorbiaceae/metabolism , Magnetic Resonance Spectroscopy , Molecular Conformation , Molecular Docking Simulation , Nitric Oxide/metabolism , Nitric Oxide Synthase Type II/metabolism , Phytochemicals/metabolism , Plant Stems/chemistry , Plant Stems/metabolism , Sesquiterpenes, Guaiane/chemistry , ThermodynamicsABSTRACT
Three new cleistanthane diterpenes named tomocinon (1), tomocinol A (2), and tomocinol B (3), were isolated from the EtOAc extract of the seed of Caesalpinia sappan. Their structures were determined by extensive NMR spectroscopic analysis. The absolute stereochemistry of tomocinon (1) has been established by CD spectroscopic analysis. Cleistanthane diterpenes (1-3) represents the novel class of antiausterity agents having preferential cytotoxicity against PANC-1 human pancreatic cancer cell line under nutrient deprived condition with PC50 value of 34.7 µM, 42.4 µM and 39.4 µM, respectively.