Chemical constituents of diterpenoids from Boswellia carterii / 中国中药杂志

This paper explored the chemical constituents of Boswellia carterii by column chromatography on silica gel, Sephadex LH-20, ODS column chromatography, and semi-preparative HPLC. The structures of the compounds were identified by physicochemical properties and spectroscopic data such as infrared radiation(IR), ultra violet(UV), mass spectrometry(MS), and nuclear magnetic resonance(NMR). Seven diterpenoids were isolated and purified from n-hexane of B. carterii. The isolates were identified as(1S,3E,7E,11R,12R)-11-hydroxy-1-isopropyl-4,8,12-trimethyl-15-oxabicyclo[10.2.1]pentadeca-3,7-dien-5-one(1),(1R,3S,4R,7E,11E)-4,8,12,15,15-pentamethyl-14-oxabicyclo[11.2.1]hexadeca-7,11-dien-4-ol(2), incensole(3),(-)-(R)-nephthenol(4), euphraticanoid F(5), dilospirane B(6), and dictyotin C(7). Among them, compounds 1 and 2 were new and their absolute configurations were determined by comparison of the calculated and experimental electronic circular dichroisms(ECDs). Compounds 6 and 7 were obtained from B. carterii for the first time.

Advances on the microbial synthesis of plant-derived diterpenoids / 生物工程学报

Natural plant-derived diterpenoids are a class of compounds with diverse structures and functions. These compounds are widely used in pharmaceuticals, cosmetics and food additives industries because of their pharmacological properties such as anticancer, anti-inflammatory and antibacterial activities. In recent years, with the gradual discovery of functional genes in the biosynthetic pathway of plant-derived diterpenoids and the development of synthetic biotechnology, great efforts have been made to construct a variety of diterpenoid microbial cell factories through metabolic engineering and synthetic biology, resulting in gram-level production of many compounds. This article summarizes the construction of plant-derived diterpenoid microbial cell factories through synthetic biotechnology, followed by introducing the metabolic engineering strategies applied to improve plant-derived diterpenoids production, with the aim to provide a reference for the construction of high-yield plant-derived diterpenoid microbial cell factories and the industrial production of diterpenoids.

Diterpenoid constituents in Pseudolarix amabilis and their antitumor activities in vitro / 中国中药杂志

By various chromatographic techniques and extensive spectroscopic methods, 17 abietane diterpenoids were isolated from the dichloromethane fraction of the 95% ethanol cold-soak extracts of the seeds of Pseudolarix amabilis, namely pseudoamaol A(1), 12α-hydroxyabietic acid(2), 12-methoxy-7,13-abietadien-18-oic acid(3), 13-hydroxy-8,11,13-podocarpatrien-18-oic acid(4), 15-hydroxy-7,13-abietadien-12-on-18-oic acid(5), 8(14)-podocarpen-13-on-18-oic acid(6), holophyllin K(7), metaglyptin B(8), 7α-hydroxydehydroabietinsaure-methylester(9), 7-oxodehydroabietic acid(10), 15-hydroxy-7-oxodehydroabietinsaure-methy-lester(11), 15-methoxydidehydroabietic acid(12), 7-oxo-15-hydroxy-dehydroabietic acid(13), 15-hydroxydehydroabietic acid(14), 8,11,13-abietatriene-15,18-diol(15), 8,11,13-abietatriene-15-hydroxy-18-succinic acid(16), and 7β-hydroxydehydroabie-tic acid(17). Compound 1 was a new compound. The isolated compounds were evaluated for their antitumor activities(HepG2, SH-SY5Y, K562), and compounds 8 and 17 showed potential cytotoxic activity against K562 cells, with IC_(50) values of 26.77 and 37.35 μmol·L~(-1), respectively.

Two new labdane diterpenoids from the leaves of Callicarpa formosana Rolfe / 药学学报

Two new labdane diterpenoids were isolated from 95% ethanol extract of the leaves of Callicarpa formosana Rolfe by using silica gel column, MCI column, ODS column and HPLC. Their structures were elucidated by HR-ESI-MS, NMR and ECD spectral data. All of them are new compounds, named 13E-6β-hydroxylabda-8(17),13-dien-15-oic acid (1) and 13E-7α-hydroxylabda-8(17),13-dien-15-oic acid (2). Compounds 1 and 2 were tested for antioxidant activity, and none of them had obvious activity.

Cost-utility analysis of pertuzumab combined with trastuzumab and docetaxel in first-line treatment of HER 2- positive metastatic breast cancer / 中国药房

OBJECTIVE To study the metabolites of four diterpenoids of Euphorbia fischeriana in liver microsomes of rats and to investigate its metabolic regularity. METHODS In vitro incubation system of liver microsomes of rats was built. The jolkinolide A，jolkinolide B ，17-hydroxyl jolkinolide A and 17-hydroxyl jolkinolide B were added into incubation system of liver microsomes in rats activated by reduced nicotinamide adenine dinucleotide phosphate ，incubated at 37 ℃ for 30 min，and then terminated the reaction with acetonitrile. Taking the negative group （adding acetonitrile firstly and then starting incubation for 30 min）as the reference，the ultra-high performance liquid chromatography-quadrupole time-of-flight mass spectrometry was used ；Anaylyst®TF 1.7.1、PeakView® 2.2，MetabolitePilot 1.5 and MasterView 1.2 software were used to speculate and identify the fragmentation law of mass spectrometry and metabolites. RESULTS Four diterpenoids were easy to lose neutral fragments such as H 2O and CO in secondary mass spectrometry. Jolkinolide A and 17-hydroxyl jolkinolide A showed similar metabolism pathway ，including dihydroxylation，dehydrogenation，and monohydroxylation ；six and five metabolites were identified respectively. Jolkinolide B and 17-hydroxyl jolkinolide B showed similar metabolism pathway ，including monohydroxylation ，hydration and isomerization. Five metabolites were identified. CONCLUSIONS Both jolkinolide A and 17-hydroxyl jolkinolide A produce the metabolites of hydroxylation and dehydrogenation in liver microsomes of rats ；both jolkinolide B and 17-hydroxyl jolkinolide B produce the metabolites of hydroxylation ，hydration and isomerization in liver microsomes of rats. The metabolites of four diterpenoids are phase Ⅰ metabolites.

Metabolism of four diterpenoids of Euphorbia fischeriana in liver microsomes of rats / 中国药房

OBJECTIVE To study the metabolites of four diterpenoids of Euphorbia fischeriana in liver microsomes of rats and to investigate its metabolic regularity. METHODS In vitro incubation system of liver microsomes of rats was built. The jolkinolide A，jolkinolide B ，17-hydroxyl jolkinolide A and 17-hydroxyl jolkinolide B were added into incubation system of liver microsomes in rats activated by reduced nicotinamide adenine dinucleotide phosphate ，incubated at 37 ℃ for 30 min，and then terminated the reaction with acetonitrile. Taking the negative group （adding acetonitrile firstly and then starting incubation for 30 min）as the reference，the ultra-high performance liquid chromatography-quadrupole time-of-flight mass spectrometry was used ；Anaylyst®TF 1.7.1、PeakView® 2.2，MetabolitePilot 1.5 and MasterView 1.2 software were used to speculate and identify the fragmentation law of mass spectrometry and metabolites. RESULTS Four diterpenoids were easy to lose neutral fragments such as H 2O and CO in secondary mass spectrometry. Jolkinolide A and 17-hydroxyl jolkinolide A showed similar metabolism pathway ，including dihydroxylation，dehydrogenation，and monohydroxylation ；six and five metabolites were identified respectively. Jolkinolide B and 17-hydroxyl jolkinolide B showed similar metabolism pathway ，including monohydroxylation ，hydration and isomerization. Five metabolites were identified. CONCLUSIONS Both jolkinolide A and 17-hydroxyl jolkinolide A produce the metabolites of hydroxylation and dehydrogenation in liver microsomes of rats ；both jolkinolide B and 17-hydroxyl jolkinolide B produce the metabolites of hydroxylation ，hydration and isomerization in liver microsomes of rats. The metabolites of four diterpenoids are phase Ⅰ metabolites.

A review: biosynthesis of plant-derived labdane-related diterpenoids / 中国天然药物

Plant-derived labdane-related diterpenoids (LRDs) represent a large group of terpenoids. LRDs possess either a labdane-type bicyclic core structure or more complex ring systems derived from labdane-type skeletons, such as abietane, pimarane, kaurane, etc. Due to their various pharmaceutical activities and unique properties, many of LRDs have been widely used in pharmaceutical, food and perfume industries. Biosynthesis of various LRDs has been extensively studied, leading to characterization of a large number of new biosynthetic enzymes. The biosynthetic pathways of important LRDs and the relevant enzymes (especially diterpene synthases and cytochrome P450 enzymes) were summarized in this review.

Research progress on chemical constituents from Chloranthus plants and their biological activities / 中国中药杂志

The genus Chloranthus has 13 species and 5 varieties in China, which can be found in the southwest and northeast regions. Phytochemical studies on Chloranthus plants have reported a large amount of terpenoids, such as diterpenoids, sesquiterpenoids, and sesquiterpenoid dimers. Their anti-inflammation, anti-tumor, antifungal, antivirus, and neuroprotection activities have been confirmed by previous pharmacological research. Herein, research on the chemical constituents from Chloranthus plants and their biological activities over the five years was summarized to provide scientific basis for the further development and utilization of Chloranthus plants.

A new labdane-type diterpenoids from Callicarpa nudiflora / 中国中药杂志

The purpose of the research is to study the bioactive constituents of Callicarpa nudiflora. From the 65% ethanol extract of C. nudiflora leaves, ten compounds were isolated by macroporous adsorption resin, Sephadex LH-20, ODS, silica gel, and preparative HPLC. These compounds were identified as callicapene M6(1), sterebin A(2), isomartynoside(3), crenatoside(4), luteolin-7-O-neohesperidoside(5), apigenin-7-O-β-D-neohesperidoside(6), isoacteoside(7), acteoside(8),(7R)-campneoside I(9), and(7S)-campneoside I(10) on the basis of NMR, HR-ESI-MS, and optical rotation data. Compound 1 was obtained as a new compound. Compounds 2 and 4 were isolated from the genus Callicarpa for the first time. Compounds 9 and 10 were isolated from C. nudiflora for the first time.

Anti-tumor Constituents from Rhizome of Euphorbia fischeriana / 中国实验方剂学杂志

Objective::To screen out active fraction from Euphorbia fischeriana, separate active components from E. fischeriana and explore structure-activity relationships, in order to analyze and identify chemical compositions of petroleum ether fraction from E. fischerian ethanol extract by ultra-performance liquid chromatography with quadrupole-time-of flight mass spectrometry (UPLC-Q-TOF-MS). Method::The anti-tumor activities of petroleum ether, ethyl acetate, n-butanol and water extracts from E. fischeriana were tested by methyl thiazolyl tetrazolium(MTT)method. A variety of modern chromatographic separation methods were used to separate active compounds from petroleum ether layer. Compounds were isolated. Their structures were identified by NMR technique. The structure-activity relationships between anti-tumor activities and structures of compounds were investigated. UPLC-Q-TOF-MS technique was used to identify the structures of petroleum ether extract from E. fischeriana. Mass spectrometry was performed in the positive ion mode using ESI ion sources. Result::Six compounds were isolated from petroleum ether fraction. They were jolkinolide A, jolkinolide B, 17-hydroxyjolkinolide A, 17-hydroxyjolkinolide B, euphopilolide and atis-16-en-13(s)-hydroxy-3, 14-dione. A total of 23 peaks were identified based on the comparison of retention times, accurate masses and fragmentation patterns with available standard compounds and literatures. Among them, there were 19 diterpenoids, 2 polyphenols, 1 fatty acid and 1 triterpenoid. Peaks No.18 and No.21 were tentatively identified as new compounds. Conclusion::The petroleum ether fraction showed a potential anti-tumor activity. The structure-activity relationships were discussed. UPLC-Q-TOF-MS technology can be used to quickly and accurately identify the structures, so as to provide a reference for its quality evaluation and active ingredient research.

Study on Chemical Constituents of Diterpenoids from Buyi Medicine Isodon coetsa / 中国药房

OBJECTIVE：To st udy the chemical constituents of diterpenoids from Buyi medicine Isodon coetsa ，and to provide reference for the development and utilization of the medicinal resources. METHODS ：The 95％ methanol extract of Buyi medicine I. coetsa were isolated and purified with silica gel column ，Sehadex LH- 20 gel column and MCI column. The structures of the compounds were obtained by spectral analysis （mass spectrum ，hydrogen spectrum and carbon spectrum ），and then compared with active components of Miao medicine “Isodon flavidus ”. RESULTS & CONCLUSIONS ：Ten diterpenoids were obtained from I. coetsa，including rabdocoetsin B （Ⅰ），megathgrin B （Ⅱ），rabdocoetsin A （Ⅲ），enanderianin N （Ⅳ），rabdocoetsin D （Ⅴ）， megathyrin A （Ⅵ），lophanic acid （Ⅶ），rubesanolide D （Ⅷ），excisanin D （Ⅸ），excisanin K （Ⅹ）. The compounds Ⅶ，Ⅸ and Ⅹ were isolated from this specie for the first time. Compound Ⅶ（lophanic acid ）is a common active component in the Buyi medicine I. coetsa and Miao medicine “I. flavidus ”.

Research progress on chemical constituents of diterpenoids of Euphorbiae Ebracteolatae Radix and its pharmacological activities / 中草药

Euphorbiae Ebracteolatae Radix is the dry root of plant Euphorbia fischeriana or E. ebracteolata of Euphorbiaceae, which is a widely utilized natural medicine with broad development prospect. It has been discovered that Euphorbiae Ebracteolatae Radix contains several biologically active constituents, among which diterpenoids are the most important. The diterpenoids of Euphorbiae Ebracteolatae Radix contain eight types including abietane-type, tigliane-type, pimarane-type, rosane-type, cembrane-type, ent-kaurane-type, ingenane-type and atisane-type. Diterpenoids of Euphorbiae Ebracteolatae Radix have significant anti-tumor, anti-inflammatory, anti-viral and other pharmacological activities. In this paper, the chemical constituents of diterpenoids and pharmacological activities of Euphorbiae Ebracteolatae Radix in recent years were reviewed in order to provide references for better developing the resources of Euphorbiae Ebracteolatae Radix and its clinical application.

Research progress on chemical constituents of Rhododendron molle and its pharmacological activities / 中草药

Rhododendron molle is a plant of the Ericaceae family. It is commonly used in the treatment of rheumatoid arthritis. Modern pharmacological studies have confirmed that its diterpenoids are main medicinal ingredients with anti-inflammatory, analgesic and other pharmacological effects. Through reviewing domestic and foreign literatures, this review aims to provide a comprehensive overview of the research progress in the chemical constituents and pharmacological effects of R. molle, and briefly prospects research of the titled plant.

Study on chemical constituents of Abies chensiensis / 中草药

Objective: To study the chemical constituents of the sterns and leaves parts of Abies chensiensis. Methods: The isolation and purification were carried out by HP-20 macroporous resin, Sephadex LH-20, silica gel column chromatography, semi-preparative HPLC. Their structures were elucidated on the basis of physicochemical properties and spectroscopic data. Results: Twenty-four compounds were isolated and elucidated from the sterns and leaves parts of A. chensiensis, their structures were identified as 7,14,24-mariesatrien-26,23-olide-3α,23-diol (1), (23R)-3α-hydroxy-9,19-cyclo-9β-lanost-24-en-26,23-olide (2), 7-oxocallitrisic acid (3), 23-hydroxy-3-oxomariesia-8 (9),14,24-trien-26,23-olide (4), neoabiestrine E (5), 3-oxo-9β-lanosta-7,24-dien-26,23R-olide (6), 7,14,22Z,24-mariesatetraen-26,23-olide-3-one (7), (+)-rel-3α-hydroxy-23-oxocycloart-25 (27)-en-26-oic acid (8), cycloart-25-en- 3β,24-diol (9), neoabiestrine H (10), 3-oxo-24,25,26,27-tetranolanost-8-en-23-oic acid (11), abiesadine C (12), 13β-epidioxy-8 (14)-abieten-18-oic acid (13), dehydroabietic acid (14), 15-hydroxydehydroabietic acid (15), methyl 18-methoxydehydroabietate (16), 7β-hydroxy dehydroabietic acid (17), dehydroabietan-18-ol (18), centdaroic acid (19), abietic acid (20), 6,8,11,13-abi-etatrien-18-oic acid (21), abiesadine B (22), abiesadine N (23), 12β-hydroxyabietic acid (24). Conclusion: All compounds are isolated from the plants of A. chensiensis for the first time, and compound 11 is isolated from the Abies genus for the first time.

Chemical constituents from Isodon amethystoides distributed in Libo / 中草药

Objective: To investigate the chemical constituents from Isodon amethystoides distributed in Libo. Methods: Chemical constituents were isolated and purified by chromatography with silica gel, MCI gel CHP 20P, and Sephadex LH-20. The structures of all compounds were elucidated by physicochemical properties, comprehensive spectral data and references. Results: Eighteen known compounds were isolated from the methanol extract of I. amethystoides, which were elucidated as lophanic acid (1), rubesanolide D (2), fladin A (3), 3,4-secoisopimara-4(18),7,15-triene-3-oic acid methylester (4), 3,4-secoisopimara-4(18),7, 15-triene-3-oic acid (5), isopimara-7,15-dien-3-one (6), isopimara-7,15-dien-3β-ol (7), alpiniol (8), (-)-clovane-2,9-diol (9), ursolic acid (10), oleanolic acid (11), epimaslinic acid (12), 7α-hydroxysitosterol (13), β-sitosterol (14), stigmasterol (15), sesamin (16), paulownin acetate (17) and dibutyl phthalate (18). Conclusion: Compound 4 is a new natural product, and compounds 2-9, 15-18 are isolated from I. amethystoides for the first time.

Taxane diterpenoids from the leaves and stems of Taxus wallichiana var. mairei / 中国药科大学学报

@#The chemical constituents of the CHCl3 extracts from the leaves and stems of Taxus wallichiana var. mairei were investigated. Twelve taxane diterpenoids were isolated and identified by spectroscopic analysis as 2-deacetoxytaxinine E (1),2-deacetoxytaxinine J (2),7-deacetoxytaxinine J (3),taxinine J (4),7,2′-didesacetoxyaustrospicatine (5),N-methyltaxol C (6),2-deacetoxydecinnamoyl taxinine J (7),taxol (8),7-epi-taxol (9),7-epi-10- deacetoxytaxol (10),cephalomannine (11),7-epi-cephalomannine (12). Compounds 1 and 3 were isolated from the leaves and stems of Taxus wallichiana var. mairei for the first time.

Cytotoxicity of naturally occurring phenolics and terpenoids from Kenyan flora towards human carcinoma cells

Background: Cancer constitutes a major hurdle worldwide and its treatment mainly relies onchemotherapy.Objectives: The present study was designed to evaluate the cytotoxicity of eleven naturally occurringcompounds including six phenolics amongst them were 4 chalcones and 2 flavanones as well as 5 terpenoids (3 clerodane and 2 trachylobane diterpenoids) against 6 human carcinoma cell lines and normalCRL2120 fibroblasts.Materials and methods: The neutral red uptake (NR) assay was used to evaluate the cytotoxicity of thecompounds, whilst caspase-Glo assay was used to detect caspase activation. Cell cycle and mitochondrialmembrane potential (MMP) were all analyzed via flow cytometry meanwhile levels of reactive oxygenspecies (ROS) was measured by spectrophotometry.Results: Chalcones: 20,40-dihydroxy-60-methoxychalcone (1); 40,60-dihydroxy-20,50-dimethoxychalcone(2); 20,40,60-trihydroxy-50-methoxychalcone (3); 20,60-diacetate-40-methoxychalcone (4), trachylobanediterpenoids: 2,6,19-trachylobanetriol; (ent-2a,6a)-form (10) and 2,18,19-trachylobanetriol; (ent-2a)-form (11) as well as doxorubicin displayed IC50 values below 110 mM in the six tested cancer cell lines. TheIC50 values of the most active compounds were between 6.30 mM and 46.23 mM for compound 1respectively towards breast adenocarcinoma MCF-7 cells and small lung cancer A549 cells and between0.07 mM and 1.01 mM for doxorubicin respectively against SPC212 cells and A549 cells. Compounds 1induced apoptosis in MCF-7 cells mediated by increasing ROS production and MMP loss.Conclusion: Chalcones 1e3 are potential cytotoxic phytochemicals that deserve more investigations todevelop novel anticancer drugs against human carcinoma.© 2018 Transdisciplinary University, Bangalore and World Ayurveda Foundation. Publishing Services byElsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

A new tricyclic abietane diterpenoid from Salvia chloroleuca and evaluation of cytotoxic and apoptotic activities

Abstract In this study, sahandone (1) and a new diterpenoid named sahandol II (2) were isolated from the roots of Salvia chloroleuca Rech. f. & Aellen, Lamiaceae. The absolute configurations of compounds 1 and 2 were assigned by comparison of experimental electronic circular dichroism spectra and comparing with published data. Cytotoxic and apoptotic evaluation of the isolated compounds and the methanol crude extract and its subfractions including petroleum ether, dichloromethane, ethyl acetate, n-butanol and aqueous fraction on two human prostate cancer cell lines and a breast cancer cell lines, showed that non-polar and semi-polar subfractions had the potent cytotoxic effect on PC3 cells with the IC50 values of 24.19, 33.59, and 47.15 µg/ml, respectively. Sub-G1 peak in flow cytometry histogram of cells treated with petroleum ether, dichloromethane and ethyl acetate subfractions showed the induction of apoptosis. Change in the Bax/Bcl-2 ratio and cleavage of poly ADP-ribose polymerase were observed.

Terpenoids isolated from Azadirachta indica roots and biological activities

Abstract The chemical study of roots from Azadirachta indica A. Juss., Meliaceae, led to the isolation of two new terpenoids, limonoid morenolide and diterpene 17-hydroxy-sandaracopimar-8,15-dien-11-one, in addition to the four well-known limonoids nimbinene, nimbinal, nimbandiol and salannin, and three diterpenoids nimbidiol, ferruginol, and 6,7-dehydroferruginol. Their structural elucidations were based on one and bidimensional Nuclear Magnetic Resonance and Electrospray ionization mass spectrometry spectra data which was compared to the data found in literature. The anti-inflammatory, cytotoxic and antimycobacterial activities of the identified terpenoids were evaluated.

Clerodane diterpenoids with potential anti-inflammatory activity from the leaves and twigs of Callicarpa cathayana / 中国天然药物

Phytochemical investigation of the leaves and twigs of Callicarpa cathayana led to the isolation of six new clerodane diterpenoids, cathayanalactones A-F (1-6), together with seven analogues (7-13). Their structures were established by extensive NMR analyses together with experimental and calculated ECD spectra analyses. Compounds 1, 2, 3, 7 and 11 showed inhibitory activities on lipopolysaccharide-induced nitric oxide production in RAW264.7 cells.