ABSTRACT
Rugosiformisin A, a skeleton-rearranged abietane-type diterpenoid with a spiro[4.5]decane motif, was isolated from Isodon rugosiformis. Its structure was unambiguously established via NMR spectroscopic analysis and single-crystal X-ray diffraction. A bioinspired asymmetric synthesis of rugosiformisin A was achieved in 15 steps with 2.7% overall yield. The synthesis features an iridium-catalyzed asymmetric polyene cyclization and a semipinacol rearrangement.
Subject(s)
Diterpenes , Isodon , Isodon/chemistry , Abietanes/chemistry , Magnetic Resonance Spectroscopy , Plant Extracts/chemistry , Skeleton , Molecular Structure , Diterpenes/chemistryABSTRACT
Two new guaianolide sesquiterpenes, lanicepines A (1) and B (2), possessing unusual amino acid-derived substituents at C-13, were isolated from the flowering aerial parts of Saussurea laniceps, a traditional herbal medicine also known as "snow lotus". The structures of 1 and 2 were elucidated based on spectroscopic analysis including applications of the modified Mosher's method and Marfey's method as well as ECD calculations. Lanicepine A (1) contains a dihydropyridinone moiety with a carbamoyl and a hydroxymethyl group. This substituent was considered to consist of asparagine and a C4 unit. In contrast, lanicepine B (2) has a substituent that seems to be derived from l-proline and a C4 unit. Lanicepines A (1) and B (2) and two related known sesquiterpenes isolated from the same plant material, 11ß,13-dihydrodesacylcynaropicrin (3) and 11ß,13-dihydrodesacylcynaropicrin 8-O-ß-d-glucoside (4), demonstrated inhibitory activity against IL-1ß production from LPS-stimulated microglial cells.
Subject(s)
Saussurea , Sesquiterpenes , Amino Acids/analysis , Molecular Structure , Plant Components, Aerial/chemistry , Saussurea/chemistry , Sesquiterpenes/chemistry , Sesquiterpenes, Guaiane/chemistryABSTRACT
Isogeopyxins A-C (1-3), three new diterpenoids with ent-kaurane, ent-pimarane, and ent-abietane scaffolds, respectively, along with six known ent-kauranoids, were isolated from the fermentation culture of Geopyxis sp. XY93 inhabiting the leaves of Isodon parvifolia. Their structures were elucidated by interpretation of spectroscopic data, and single crystal X-ray diffraction. It marks the first time that ent-kauranoids, characteristic metabolites of Isodon species, have been isolated from an associated endophytic fungus.
Subject(s)
Antineoplastic Agents, Phytogenic , Ascomycota , Diterpenes, Kaurane , Diterpenes , Isodon , Antineoplastic Agents, Phytogenic/chemistry , Drug Screening Assays, Antitumor , Isodon/chemistry , Molecular StructureABSTRACT
Eleven undescribed schinortriterpenoids (SNTs) and one known analogue (12) were isolated from the stems and leaves of Schisandra henryi. Their diverse structures included preschisanartane (1), 18-norschiartane (2-5, 12), schiartane (6 and 7), and schisanartane (8-11) skeletons, which were elucidated by comprehensive NMR, MS, electronic circular dichroism analyses, single crystal X-ray diffraction and biogenetic considerations. 1 was the first case of preschisanartane-type SNT with six-membered lactone ring, and 2 was one of the most highly oxygenated 18-norschiartane SNTs. Three types of the highly oxygenated SNTs, 1, 4, 10 and 11, effectively prevent apoptosis induced by corticosterone in PC12 cells. In addition, 11 showed neurite outgrowth-promoting activity.
Subject(s)
Neuroprotective Agents/chemistry , Plant Extracts/chemistry , Plant Leaves/chemistry , Plant Stems/chemistry , Schisandra/chemistry , Triterpenes/chemistry , Animals , Corticosterone/metabolism , Drug Evaluation, Preclinical , Humans , Lactones/chemistry , Molecular Structure , Neuroprotective Agents/pharmacology , Oxygen/chemistry , PC12 Cells , Rats , Triterpenes/pharmacologyABSTRACT
Six new ent-kaurane diterpenoids, isorugosiformins A-F (1-6), were isolated from the aerial parts of Isodon rugosiformis Hand.-Mazz. Hara. Their structures were elucidated by spectroscopic data interpretation, single crystal X-ray diffraction, and quantum chemical calculation of NMR parameters. The absolute configuration of 5 as 6R was the first case in the known 6,7:8,15-diseco-7,20-olide-6,8-cyclo-ent-kaurane diterpenoids.
Subject(s)
Diterpenes, Kaurane/isolation & purification , Isodon/chemistry , Animals , Cell Line, Tumor , Diterpenes, Kaurane/chemistry , Drug Screening Assays, Antitumor , Humans , Mice , RAW 264.7 CellsABSTRACT
Four new ent-abietane diterpenoids, isoforrethins A-D (1-4), were isolated from the aerial parts of Isodon forrestii var. forrestii by a variety of chromatographic techniques. Their structures were elucidated on the basis of spectroscopic data interpretation, single crystal X-ray diffraction, and quantum chemical calculation. All of these compounds were evaluated for their cytotoxicity against five human tumor cell lines (HL-60, SMMC-7721, A-549, MCF-7 and SW-480), and compound 4 showed significant inhibitory activities against SMMC-7721, A-549, MCF-7, and SW-480.
Subject(s)
Abietanes/pharmacology , Isodon/chemistry , Abietanes/isolation & purification , Antineoplastic Agents, Phytogenic , Cell Line, Tumor , China , Humans , Molecular Structure , Phytochemicals/isolation & purification , Phytochemicals/pharmacology , Plant Components, Aerial/chemistryABSTRACT
Two new ent-clerodane diterpenoids, named isoscoparins R and S (1 and 2), were isolated from the aerial parts of Isodon scoparius. Their structures were characterized mainly by analyzing the NMR and HRESIMS data, and the relative configuration of compound 1 was determined by single-crystal X-ray diffraction. Compound 2 showed weak activity as an autophagic inhibitor.
Subject(s)
Diterpenes, Clerodane/chemistry , Diterpenes, Clerodane/pharmacology , Isodon/chemistry , Antineoplastic Agents, Phytogenic/chemistry , Autophagy/drug effects , Drug Screening Assays, Antitumor , Drugs, Chinese Herbal/chemistry , HEK293 Cells , HeLa Cells , Humans , Immunosuppressive Agents/pharmacology , Magnetic Resonance Spectroscopy , Molecular Structure , Plant Components, Aerial/chemistry , Spectrometry, Mass, Electrospray Ionization , X-Ray DiffractionABSTRACT
Nine new ent-kaurane diterpenoids, named scopariusols L-T (1-9), were isolated from the aerial parts of Isodon scoparius. Their structures were characterized mainly by analyzing the NMR and HR-ESI-MS data, and the absolute configuration of 1 was determined by single-crystal X-ray diffraction. Compound 1 was active against five human tumor cell lines (HL-60, SMMC-7721, A-549, MCF-7, and SW-480), and it also inhibited NO production in LPS-stimulated RAW264.7 cells, with an IC50 value of 0.6 µmol·L-1.
Subject(s)
Antineoplastic Agents, Phytogenic/chemistry , Diterpenes, Kaurane/chemistry , Drugs, Chinese Herbal/chemistry , Isodon/chemistry , Animals , Antineoplastic Agents, Phytogenic/isolation & purification , Antineoplastic Agents, Phytogenic/pharmacology , Cell Line, Tumor , Crystallography, X-Ray , Diterpenes, Kaurane/isolation & purification , Diterpenes, Kaurane/pharmacology , Drug Screening Assays, Antitumor , Drugs, Chinese Herbal/isolation & purification , Drugs, Chinese Herbal/pharmacology , HL-60 Cells , Humans , Lipopolysaccharides/pharmacology , Macrophages/drug effects , Mice , Molecular Structure , Nitric Oxide/biosynthesis , Nuclear Magnetic Resonance, Biomolecular , Plant Components, Aerial/chemistry , RAW 264.7 CellsABSTRACT
Five new compounds, rigenolides D-H (1-5), were isolated from the aerial parts of Gentiana rigescens Franch. Their structures were assigned by detailed spectroscopic analyses and chemical conversions. Rigenolides D (1) and E (2) were elucidated to be a secoiridoid and a norsecoiridoid, respectively, possessing a dienone moiety in common. Rigenolides F-H (3-5) were assigned as acylated secoiridoid glucosides.
Subject(s)
Gentiana/chemistry , Iridoids/chemistry , Plant Extracts/chemistry , Molecular StructureABSTRACT
Five new schinortriterpenoids, propinqtrilactones A and B (1 and 2) with rare lancischiartane scaffold, and propindilactones V-X (3-5), were isolated from the stems and leaves of Schisandra propinqua var. propinqua. Their structures were elucidated on the basis of comprehensive spectroscopic and mass spectrometric analysis. The absolute configurations of 1-5 were determined by CD methods, X-ray diffraction analysis and theoretical calculations. 4 was tested for its cytotoxic activities against five human tumor cell lines.
Subject(s)
Schisandra/chemistry , Triterpenes/isolation & purification , Cell Line, Tumor , Circular Dichroism , Crystallography, X-Ray , Humans , Molecular Structure , Plant Leaves/chemistry , Plant Stems/chemistryABSTRACT
Plants belonging to the genus Leonurus, also named motherwort, are traditionally used for anti-gynecological disorder in East Asia, and for sedative in Europe. Chemical investigation of the genus Leonurus not only enriched the natural products library, but also enlarged the pharmacological application of this traditional herb. In this review, we systematically summarized the structures of 259 compounds isolated from the genus Leonurus, featured with 147 labdane diterpenoids. The reported bioactivity studies up to 2017 are presented in the second part, with the main focus on the isolated compounds and also concerning the extracts. In addition to the traditional uterine contraction and sedative activity, recently the cardiovascular protection effect of leonurine has drawn most attention. Other than that, neuroprotection, anti-inflammation, anti-cancer, anti-platelet aggregation and many other activities have been assigned to various compounds from the genus Leonurus. Among 70 bioactivity references cited in this review, 57% of them were concentrated on two alkaloids (leonurine and stachydrine), whereas only 20% are about the 147 diterpenoids. Anti-inflammation is the major bioactivity discovered so far for the labdane diterpenoids from the genus Leonurus, whose further therapeutic potential still remains for exploration.
Subject(s)
Anti-Inflammatory Agents/pharmacology , Diterpenes/pharmacology , Leonurus/chemistry , Phytochemicals/pharmacology , Anti-Inflammatory Agents/chemistry , Anti-Inflammatory Agents/isolation & purification , Diterpenes/chemistry , Diterpenes/isolation & purification , Humans , Phytochemicals/chemistry , Phytochemicals/isolation & purification , Plant Extracts/chemistryABSTRACT
A phytochemical investigation of an ethyl acetate extract of the aerial parts of Isodon pharicus led to the isolation of 21 new 7α,20-epoxy-ent-kaurane diterpenoids, pharicins C-W (1-21), and 29 known (22-50) analogues. The structural characterization of 1-21 and assignment of their relative configurations were accomplished by spectroscopic data interpretation, while the structures of 1 and 16 were confirmed by X-ray crystallography. The absolute stereostructure of 1 was confirmed by electronic circular dichroism data analysis. Twenty-five of the diterpenoids were screened for their cytotoxic activities against a panel of tumor cell lines, including HL-60, SMMC-7721, A-549, MCF-7, and SW-480. Compounds 11, 16, 38, and 48 exhibited inhibitory activities against these tumor cell lines with IC50 values ranging from 1.01 to 9.62 µM, while 2, 15, 29, and 47 exhibited moderate cytotoxic potency.
Subject(s)
Diterpenes, Kaurane/chemistry , Isodon/chemistry , Antineoplastic Agents, Phytogenic/chemistry , Antineoplastic Agents, Phytogenic/pharmacology , Cell Line, Tumor , Crystallography, X-Ray/methods , Diterpenes, Kaurane/pharmacology , Drug Screening Assays, Antitumor , Drugs, Chinese Herbal/chemistry , Drugs, Chinese Herbal/pharmacology , HL-60 Cells , Humans , MCF-7 Cells , Plant Components, Aerial/chemistryABSTRACT
Seven previously undescribed 7,20-epoxy-ent-kaurane diterpenoids, isojiangrubesins A-G, along with seventeen known ones, were isolated from the aerial parts of Isodon rubescens. Their structures were characterized on the basis of spectroscopic methods and signal-crystal X-ray diffraction. All of these compounds were evaluated for their in vitro cytotoxicity against five human tumor cell lines (HL-60, SMMC-7721, A-549, MCF-7, and SW480). Four isolates exhibited significant inhibitory ability against all cell lines, with IC50 values ranging from 0.5 to 6.5 µM; They also strongly inhibited NO production in LPS-stimulated RAW264.7 cells.
Subject(s)
Antineoplastic Agents, Phytogenic/isolation & purification , Antineoplastic Agents, Phytogenic/pharmacology , Diterpenes, Kaurane/isolation & purification , Diterpenes, Kaurane/pharmacology , Drugs, Chinese Herbal/isolation & purification , Drugs, Chinese Herbal/pharmacology , Isodon/chemistry , Antineoplastic Agents, Phytogenic/chemistry , Crystallography, X-Ray , Diterpenes, Kaurane/chemistry , Drug Screening Assays, Antitumor , Drugs, Chinese Herbal/chemistry , HL-60 Cells , Humans , Lipopolysaccharides/pharmacology , Macrophages/drug effects , Molecular Structure , Nitric Oxide/biosynthesis , Plant Components, Aerial/chemistryABSTRACT
Fourteen new diterpenoids (1-14) based on four skeletal types and two known analogues (15 and 16) were isolated from the aerial parts of Isodon scoparius. Compound 2 is the first ent-kaurane diterpenoid featuring a 1,11-ether bridge, and the structures of these new compounds were established mainly by NMR and MS methods. The absolute configurations of 1 and 5 and the relative configuration of 3 were determined using single-crystal X-ray diffraction. The absolute configuration of 14 was determined by comparison of the experimental and calculated electronic circular dichroism spectra. Compounds 1, 4, and 15 were active against five human tumor cell lines (HL-60, SMMC-7721, A-549, MCF-7, and SW-480), and they also inhibited NO production in LPS-stimulated RAW264.7 cells, with IC50 values of 1.0, 3.1, and 1.8 µM, respectively.
Subject(s)
Antineoplastic Agents, Phytogenic , Diterpenes, Kaurane , Isodon/chemistry , Plant Components, Aerial/chemistry , Antineoplastic Agents, Phytogenic/chemistry , Antineoplastic Agents, Phytogenic/isolation & purification , Antineoplastic Agents, Phytogenic/pharmacology , Crystallography, X-Ray , Diterpenes, Kaurane/chemistry , Diterpenes, Kaurane/isolation & purification , Diterpenes, Kaurane/pharmacology , Drug Screening Assays, Antitumor , Drugs, Chinese Herbal/chemistry , Drugs, Chinese Herbal/isolation & purification , Drugs, Chinese Herbal/pharmacology , HL-60 Cells , Humans , Lipopolysaccharides/pharmacology , Macrophages/drug effects , Molecular Structure , Nitric Oxide/biosynthesis , Nuclear Magnetic Resonance, BiomolecularABSTRACT
Sixteen dibenzocyclooctadiene lignans, including eight new ones, kadheterins A-H (1-8), and a new natural product, 9-benzoyloxy-gomisin B (9), were isolated from the stems of K. heteroclita. The structures of 1-9 were elucidated by extensive spectroscopic methods, and their absolute configurations were determined by combining CD with ROESY experiments. Additionally, the absolute configuration of 1 was further confirmed by single crystal X-ray crystallographic analysis. In vitro activity assays showed that 1 exhibited moderate cytotoxicity against HL-60 with IC50 value at 14.59µM.
Subject(s)
Cyclooctanes/chemistry , Kadsura/chemistry , Lignans/chemistry , Animals , Cell Line, Tumor , Cyclooctanes/isolation & purification , HL-60 Cells , Humans , Lignans/isolation & purification , Macrophages/drug effects , Mice , Molecular Structure , Nitric Oxide/metabolism , Plant Stems/chemistry , RAW 264.7 CellsABSTRACT
Four new ent-abietane diterpenoids, along with four known ones were isolated from the aerial parts of Isodon serra, a traditional Chinese folk medicine. The new diterpenoids were named as serrin K (1), xerophilusin XVII (2), and enanderianins Q and R (3 and 4), while the known ones were identified as rubescansin J (5), (3α,14ß)-3,18-[(1-methylethane-1,1-diyl)dioxy]-ent-abieta-7,15(17)-diene-14,16-diol (6), xerophilusin XIV (7), and enanderianin P (8), respectively. Their structures were elucidated by extensive spectroscopic analysis and comparison with the literature. Compound 1 showed remarkable inhibitory activity towards NO production in LPS-stimulated RAW264.7 cells (IC50 = 1.8 µM) and weak cytotoxicity towards five human tumor cell lines (HL-60, SMMC-7721, A-549, MCF-7, SW480).
Subject(s)
Abietanes/chemistry , Abietanes/isolation & purification , Isodon/chemistry , Plant Extracts/chemistry , Plant Extracts/isolation & purification , Abietanes/pharmacology , Animals , Antineoplastic Agents, Phytogenic/chemistry , Antineoplastic Agents, Phytogenic/pharmacology , Cell Line , Cell Line, Tumor , Humans , Macrophages/drug effects , Macrophages/metabolism , Magnetic Resonance Spectroscopy , Mice , Models, Molecular , Molecular Conformation , Molecular Structure , Nitric Oxide/biosynthesis , Plant Components, Aerial/chemistry , Plant Extracts/pharmacologyABSTRACT
Fourteen new rearranged 6/6/5/6-fused triterpenoid acids, namely, kadcoccine acids A-N (1-14), were isolated from an EtOAc-soluble extract of the stems of Kadsura coccinea. Their structures were characterized mainly by analyzing 1D and 2D NMR and HRESIMS data and were shown to feature a rare 14(13â12)-abeo-lanostane skeleton. Compounds 7 and 8 represented the first examples of a 5-substituted 2(5H)-furanone motif on the C-17 side chain of this skeleton. The absolute configurations of C-23 for compounds 1, 7, and 8 were determined by comparison of their experimental electronic circular dichroism spectra. All the isolates were screened for their in vitro cytotoxicity against six human tumor cell lines (HL-60, SMMC-7721, A-549, MCF-7, SW-480, and HeLa), and compounds 2 and 8 exhibited weak inhibitory effects with IC50 values ranging from 3.11 to 7.77 µM.
Subject(s)
Antineoplastic Agents, Phytogenic/chemistry , Antineoplastic Agents, Phytogenic/isolation & purification , Drugs, Chinese Herbal/chemistry , Drugs, Chinese Herbal/isolation & purification , Kadsura/chemistry , Plant Stems/chemistry , Triterpenes/chemistry , Triterpenes/isolation & purification , Antineoplastic Agents, Phytogenic/pharmacology , Cell Survival/drug effects , Drug Screening Assays, Antitumor , Drugs, Chinese Herbal/pharmacology , Female , HL-60 Cells , HeLa Cells , Humans , Lanosterol/chemistry , MCF-7 Cells , Molecular Structure , Nuclear Magnetic Resonance, Biomolecular , Structure-Activity Relationship , Triterpenes/pharmacologyABSTRACT
YinHuang drop pill (YHDP) is a new preparation, derived from the traditional YinHuang (YH) decoction. Since drop pills are one of the newly developed forms of Chinese patent drugs, not much research has been done regarding the quality and efficacy. This study aims to establish a comprehensive quantitative analysis of the chemical profile of YHDP. ultra high-performance liquid chromatography quadrupole time of flight mass spectrometry (UHPLC-Q-TOF-MS/MS) was used to identify 34 non-sugar small molecules including 15 flavonoids, 9 phenolic acids, 5 saponins, 1 iridoid, and 4 iridoid glycosides in YHDP samples, and 26 of them were quantitatively determined. Sugar composition of YHDP in terms of fructose, glucose and sucrose was examined via a high performance liquid chromatography-evaporative light scattering detector on an amide column (HPLC-NH2P-ELSD). Macromolecules were examined by high performance gel permeation chromatography coupled with ELSD (HPGPC-ELSD). The content of the drop pill's skeleton component PEG-4000 was also quantified via ultra-high performance liquid chromatography coupled with charged aerosol detector (UHPLC-CAD). The results showed that up to 73% (w/w) of YHDP could be quantitatively determined. Small molecules accounted for approximately 5%, PEG-4000 represented 68%, while no sugars or macromolecules were found. Furthermore, YHDP showed no significant differences in terms of daily dosage, compared to YinHuang granules and YinHuang oral liquid; however, it has a higher small molecules content compared to YinHuang lozenge.
Subject(s)
Chromatography, High Pressure Liquid/methods , Drugs, Chinese Herbal , Mass Spectrometry/methodsABSTRACT
Thirty-two enmein-type ent-kaurane diterpenoids, including 13 new compounds, were isolated from the aerial parts of Isodon phyllostachys. Compounds 1 and 2 are the first examples of 3,20:6,20-diepoxyenmein-type ent-kauranoids, and the structures of these new compounds were established mainly by analyzing NMR and HREIMS data. The absolute configurations of 1 and 8 and the relative configuration of 9 were determined using single-crystal X-ray diffraction. Compounds 11, 15, 20, and 21 were active against five human cancer cell lines (HL-60, SMMC-7721, A-549, MCF-7, and SW-480), with IC50 values ranging from 1.2 to 5.0 µM. Compounds 3, 11, 15, 17, 20, 21, 25, and 29 strongly inhibited NO production in LPS-stimulated RAW264.7 cells, with IC50 values ranging from 0.74 to 4.93 µM.
Subject(s)
Antineoplastic Agents, Phytogenic/isolation & purification , Antineoplastic Agents, Phytogenic/pharmacology , Diterpenes, Kaurane/isolation & purification , Diterpenes, Kaurane/pharmacology , Drugs, Chinese Herbal/isolation & purification , Drugs, Chinese Herbal/pharmacology , Isodon/chemistry , Animals , Antineoplastic Agents, Phytogenic/chemistry , Crystallography, X-Ray , Diterpenes , Diterpenes, Kaurane/chemistry , Drug Screening Assays, Antitumor , Drugs, Chinese Herbal/chemistry , HL-60 Cells , Humans , Inhibitory Concentration 50 , Lipopolysaccharides/pharmacology , Mice , Molecular Conformation , Molecular Structure , Nitric Oxide/biosynthesis , Plant Components, Aerial/chemistryABSTRACT
Twenty new neo-clerodane type diterpenoids, scutefolides G1-S (1-20), were isolated from the 70 % aqueous acetone extract of the aerial parts of Scutellaria coleifolia. Their structures were elucidated by extensive spectroscopic analyses. The absolute configurations of 1, 2, 7, 8, 14 and 15 were determined by means of the CD exciton chirality method. Compounds 1, 2, 5, 7, 8, 12, 14, 15, 18 and 19 were evaluated for their cytotoxic activities against four human cancer cell lines, and anti-bacterial activities against methicillin-resistant Staphylococcus aureus.