Clerodane diterpenes from Baccharis sagittalis: insect antifeedant activity

Two clerodane-type diterpene glycosides esters, which were studied as peracetyl derivatives, together with the known diterpene marrubiagenine, were isolated from the aerial part of Baccharis sagittalis (Less). Their structures were established by spectroscopic methods. Antifeedant activity toward Tenebrio molitor larvae of the isolated compounds along with six other diterpenes was evaluated and some structure-antifeedant bioactivity relationships are reported.     

Non-polar and polar chemical profiling of six Casearia species (Salicaceae)

Six species of Casearia (C. decandra, C. grandiflora, C. javitensis, C. arborea, C. lasiophylla and C. ulmifolia) were chemically investigated in their non-polar and polar constituents. To this purpose, leaf extracts were analyzed by Gas- (GC) and Liquid-Chromatography (LC) coupled with Mass Spectrometry (MS). Twenty compounds, mainly identified as terpenes, fatty acids and hydrocarbons, and differentially expressed in the six species, were detected in the non-polar extracts. Fourteen compounds, among which glycosylated flavonoids and clerodane-type diterpenes, were tentatively identified by LC-MS/MS analysis in the leaf ethanol extracts.     

Schistosomicidal activity of kaurane,labdane and clerodane-type diterpenes obtained by fungal transformation

Schistosomiasis continues to be a huge challenge for researchers, pharmaceutical companies, and governments in developing countries. Diterpene compounds are good source for the development of novel potential leading compounds to treat schistosomiasis. We are reporting herein the schistosomicidal activity of ent-kaurenoic acid, ent-copalic acid, ent-hardwickiic acid, isolated from oleoresins of Copaifera spp, and of their derivatives obtained by fungal transformation with strains of Aspergillus fumigatus, A. terreus, A. phoenicis and A. ochraceus, and of Cunninghamella echinulata e C. elegans. The in vitro antiparasitical assays were performed using adult worm pairs of Schistosoma mansoni for the evaluation of the worm pairing, egg production, and eggs development. Ten kaurane, labdane and clerodane-type diterpenes were obtained by fungal transformation and 7α-acetoxy-ent-kaur-16-en-19-oic acid and ent-hardwickiic acid were the most active ones by causing mortality of 100 % of the parasites within 24 h (concentrations of 100.0 and 200.0 μM) and displaying respective IC₅₀ values for 24, 48 and 72 h of 56.7, 37.6 and 29.2 μM and 29.6, 30.8 and 25.7 μM. Additionally, 7α-acetoxy-ent-kaur-16-en-19-oic acid and ent-hardwickiic acid highly reduced the number of laid eggs at 6.25 and 12.5 μM, respectively. These diterpenes should be further investigated as potential candidates for antiparasitic drug discovery.     

Isolation and structure of stephalic acid,a new clerodane diterpene from Stevia polycephala

From the methanolic extract of Stevia polycephala a new clerodane-type diterpene, stephalic acid, was isolated. The structure and stereochemistry were determined by a combination of spectral data and single-crystal X-ray analysis.     

Establishment of callus,cell suspension and shoot cultures of Leonurus cardiaca L. and diterpene analysis

Summary Callus cultures, cell suspension cultures and shoot cultures of Leonurus cardiaca L. (Motherwort) were established and growth conditions optimized. Shoot cultures showed constant growth whether in the dark or under continuous light, accumulating varying amounts of the furanic labdane diterpenes leosibiricin, preleosibirin, leosibirin and isoballotenol acetate, which are also present in the soil-grown plants. Only traces of leosibiricin were detected in callus cultures, while cell suspension cultures did not produce any furanic diterpenes. A small amount of furanic labdane diterpenes was found in the medium of shoot cultures. Callus and shoot culture induction of several other Lamiaceae species is also described.Abbreviations 2 4-D 2,4-dichlorophenoxyacetic acid - BAP benzylaminopurine - GA₃ gibberellic acid - HPLC high pressure liquid chromatography - NAA naphthyl acetic acid - TLC thin layer chromatography     

Tagalsins A-H, dolabrane-type diterpenes from the mangrove plant, Ceriops tagal

From the stems and twigs of the mangrove plant, Ceriops tagal, seven dolabrane-type diterpenes, namely tagalsins A-G (1-7), and the norditerpene tagalsin H (8) were isolated. Their structures were established on the basis of extensive spectroscopic analysis.     

Pimarane diterpenes: Natural source,stereochemical configuration,and biological activity

Plants and fungi are seemingly inexhaustible sources of interesting natural products with remarkable structural and biological diversity. One of the most important groups is the terpenes, ubiquitous natural products that are generated by 2 now well‐established biosynthetic pathways: the older mevalonate and the more recently discovered 1‐deoxyxylulose‐5‐phosphate. Among the diterpenes, the pimarane diterpenes are a very representative subgroup with several and interesting biological activities resulting from different functional group modifications. In this review, we outline the method of their structure determination, mainly spectroscopic results, their absolute configuration, and structure‐activity relationships, were reported, as well as the mode of action for selected examples from plants, marine organisms, and fungi. The pimarane, isopimarane, and ent‐pimarane diterpenes covered in this review have a wide range of biological activities including antimicrobial, antifungal, antiviral, phytotoxic, phytoalexin, cytotoxicity, and antispasmodic and relaxant effects.     

Flavonoids and terpenoids from the resinous exudates of Madia species (Asteraceae,Helenieae)

The resinous material accumulated on aerial parts of Madia species is shown to consist mainly of diterpenes, containing a series of flavonoid aglycones. A6- and/or 8-O-substitution is characteristic for many of these flavonoids. Three known rare diterpenes were found and the structure elucidation of a diterpene with a new carbon skeleton, named madiaol, is reported.     

Effects of six diterpenes on macrophage eicosanoid biosynthesis

Six diterpenes (three clerodanes, two abietanes and one rosane) were tested for interactions with the cyclooxygenase and 5-lipoxygenase pathways of arachidonate metabolism and for effects of nitric oxide production. Two abietane diterpenes, aethiopinone and 11,12-dihydroxy-6-oxo-8,11,13-abietatriene and the rosane lagascatriol showed a remarkable effect on COX-1 pathway of PGE2 release in calcium ionophore A23187-stimulated peritoneal macrophages. Only the two latter diterpenes showed inhibition on COX-2 pathway of PGE2 release in E. coli LPS-stimulated peritoneal macrophages. In addition, all compounds assayed were inhibitors of LTC4 release with IC50 < or = 10 microM. Clerodane diterpenes were inactive in COX assay. None of the diterpenes assayed, except 11,12-dihydroxy-6-oxo-8,11,13-abietatriene, affected NO production. The results obtained suggest that the cellular mechanisms of action of some of these substances may involve inhibition of cyclooxygenase/lipoxygenase pathways and nitric oxide production.     

Macrocyclic diterpenes from Euphorbia nivulia

The latex of Euphorbia nivulia afforded two ingol diterpenes 3,12-diacetyl-8-benzoylingol (4) and 3,12-diacetyl-7-benzoyl-8-nicotinylingol (5) along with three known ingol diterpenes 1, 2,and 3, and two known triterpenes cycloart-25-en-3beta-ol and cyclonivulinol. Their structures have been assigned on the basis of their structural data as well as their acetylated products. The diterpenes 1-5 were tested for the LPS induced PGE(2) inhibition activity.     

Abietane diterpenes induce cytotoxic effects in human pancreatic cancer cell line MIA PaCa-2 through different modes of action

Abietane diterpenes, especially those containing quinone moieties, are often reported to have cytotoxic effects on cancer cell lines. They deserve greater attention because several cancer chemotherapeutic agents also possess the quinone structural feature. To date, very little is known about their cytotoxic molecular modes of action. In the present study, five diterpenes, 7 alpha-acetoxyroyleanone, horminone, royleanone, 7-ketoroyleanone and sugiol which have been previously isolated from the medicinal plant Peltodon longipes were shown to possess cytotoxic activity against the human pancreatic cancer cell line MIA PaCa-2. 7 alpha-Acetoxyroyleanone, horminone and royleanone were demonstrated to possess alkylating properties using the nucleophile 4-(4-nitrobenzyl)pyridine. However, no clear correlation between the alkylating properties and cytotoxicity of these diterpenes was observed. Furthermore, the relaxation activity of human DNA topoisomerases I and II was found to be influenced by these compounds, with 7-ketoroyleanone and sugiol being the most active. These two diterpenes preferentially inhibited topoisomerase I and exhibited lower IC₅₀ values than the classical topoisomerase I inhibitor camptothecin. Molecular docking studies revealed possible interactions of diterpenes with topoisomerase I, indicating that these compounds do not form the drug–enzyme–DNA covalent ternary complex as observed with camptothecin. A binding pocket located at the surface of the DNA-interaction site was proposed. Moreover, the ability of the five diterpenes to generate DNA-strand breaks in single cells was confirmed using the alkaline comet assay. As expected, these diterpenes also influenced cell cycle progression and arrested cells in different phases of the cell cycle, primarily the G1/G0 and S-phases. Interestingly, the diterpenes only exhibited a slight ability to induce apoptotic cell death and failed to generate intracellular reactive oxygen species. These results provide additional understanding of the cytotoxic effects of abietane diterpenes. Depending on their functional groups, we propose that abietane diterpenes utilise different mechanisms to induce cell death.     

Synthesis of 1-O-monoacyl or 12-O-monoacyl, 1-,12-O-diacyl-, and 11,12-dehydrated excisanin A 7,14-acetonides and their cytotoxic activity

1-O-Monoacyl, 12-O-monoacyl, 1-,12-O-diacyl, and 11,12-dehydrated excisanin A 7,14-acetonides were synthesized from excisanin A isolated from Rabdosia excisa. The structure and cytotoxic activity relationships (SAR) of the natural parent ent-kaurene diterpenes and these semisynthetic analogues were studied by using P388 murine leukemia cells.     

Phytane and neoclerodane diterpenes from the aerial parts of Inula nervosa Wall.

Three new aliphatic diterpenes (1–3), together with three known neoclerodane-type diterpenes (4–6) were isolated from the aerial parts of Inula nervosa Wall. The structures of 1-3 were elucidated on the basis of 1D and 2D spectroscopic analysis. Additionally, phytane-type and neoclerodane-type diterpenes have not been reported in any species of the genus Inula yet. The phytane-type and neoclerodane-type diterpenes obtained from I. nervosa Wall. suggest this plant maybe have remote genetic relations with other Inula species.     

Structures, biogenetic relationships, and cytotoxicity of pimarane-derived diterpenes from Petalostigma pubescens

Extraction of Petalostigma pubescens heartwood followed by chromatographic purifications and crystallizations afforded five tricyclic diterpenes: 5,9-syn-rosanes petalostigmones A and B (1 and 2), the erythroxylane petalostigmone C (3), the norditerpene lactone pubescenone (4), and the known ent-cleistanthane diterpene (-)-sonderianol (5). The structures and relative stereochemistry were elucidated by means of spectroscopic methods, chemical correlations, and, in the cases of 1 and 4, by X-ray crystallographic analyses. The new isolates 1-4 are assumed to belong to the same absolute configurational family (9alphaCH3) of ent-pimarane-derived diterpenes as the known co-occurring (-)-5 (10alphaCH3). Biogenetic schemes originating from a common ent-copalyl diphosphate intermediate are presented to rationalize the structures of these natural products. A novel ring contraction-ring expansion mechanism is suggested to account for the 7-membered B ring of pubescenone. Compounds 1-5 were evaluated for their cytotoxicity; sonderianol (5) showed the highest activity against mouse leukemia cell lines L1210, P388 and mouse liver cancer cells HEPA1c1c7.     

Changes in carotenoids, tocopherols and diterpenes during drought and recovery, and the biological significance of chlorophyll loss in Rosmarinus officinalis plants

Two-year-old rosemary (Rosmarinus officinalis L.) plants were subjected to severe stress by exposure to prolonged drought during a Mediterranean summer. Severely stressed plants recovered completely after the autumn rainfalls although the relative water content remained below 35% for 3 months and the chlorophyll content of leaves was reduced by up to 85% during the drought. In severe stress: (i) α-tocopherol increased 9-fold per g dry weight and 20-fold per unit of chlorophyll; (ii) lutein and β-carotene contents decreased on a dry-weight basis, but an 80% increase in lutein and constant levels of β-carotene were observed on a chlorophyll basis; (iii) there were transient and sustained increases in the de-epoxidation state of the xanthophyll cycle; and (iv) the highly oxidised abietane diterpene isorosmanol increased 8-fold as a result of the oxidation of carnosic acid. With the autumn rainfalls, water status, α-tocopherol and violaxanthin recovered first and the levels of photosynthetic pigments and abietane diterpenes increased later. The photoprotection conferred by the xanthophyll cycle and the antioxidant function of tocopherols, lutein and diterpenes may help to avoid irreversible damage in severe drought, making possible the recovery of functional membranes after the autumn rainfalls. Besides, chlorophyll loss reduces the amount of photons absorbed by leaves, which enhances the photoprotective and antioxidant capacity of leaves per amount of photons absorbed, since the ratios of xanthophylls, α-tocopherol and abietane diterpenes to chlorophyll increase. Received: 12 July 1999 / Accepted: 25 November 1999     

Taxodistines A and B, abietane-type diterpenes from Taxodium distichum

Two new abietane-type diterpenes, taxodistines A (1) and B (2), have been isolated by the guidance of inhibitory effect of tubulin polymerization from the fruits of Taxodium distichum and the structures were elucidated by using 2D NMR data. Taxodistine B (2) showed inhibition of tubulin polymerization.     

Diterpenes from Dictyota dichotoma

Two new and two known diterpenes were isolated from Dictyota dichotoma. The structures of the new diterpenes were elucidated from spectral and X-ra     

A comparative phytochemical study of the diterpenes of some species of the genera Euphorbia and Elaeophorbia (Euphorhiaceae)

Nearly 60 species from the genera Euphorbia L. and Elaeophorbia Stapf were investigated for diterpenes of the classes tiglianes, ingenanes and ortho-esters. The diterpenes were isolated as their acetates by a micro-technique from latex or fresh herb material collected from several countries around the world. Authentication of the diterpenes was by chromatographic means using spectroscopic methods as back-up data. These compounds were absent from only 9% of the species examined. The most commonly occurring diterpene was ingenol, followed closely by 12-Deoxy phorbol. The ingenane derivative 5-Deoxy-ingenol was always detected as a minor companion to ingenol from species of the section Tithymalus. Species of the section Euphorbium contained mainly the diterpene ingenol although both tigliane and ortho-ester diterpenes were also present in some species. Species from the sections Anisophylhtm and Poinsettia did not contain diterpenes of the type in question, whilst species from the genus Elaeophorbia yielded ingenol. These results provide additional chemical evidence concerning recent suggestions on the subgeneric and generic status of Anisophyllum, Poinsettia, Tithymalus and Elaeophorbia.     

Conidiogenones H and I, two new diterpenes of Cyclopiane class from a marine-derived endophytic fungus Penicillium chrysogenum QEN-24S

Two new tetracyclic diterpenes of the rarely reported cyclopiane class, conidiogenones H and I ( 1 and 2 , resp.), along with five related congeners, conidiogenones B – D and F ( 3 – 5 and 6 , resp.) and conidiogenol ( 7 ), were characterized from the culture extracts of Penicillium chrysogenum QEN‐24S, an endophytic fungus derived from an unidentified marine red algal species of the genus Laurencia. The structures of these compounds were established on the basis of extensive spectroscopic analysis. The inhibitory activity of theses diterpenes against four bacteria and one pathogen fungus was evaluated. Conidiogenone B ( 3 ) showed potent activity against Methicillin resistant Staphylococcus aureus (MRSA), Pseudomonas fluorescens, P. aeruginosa, and Staphylococcus epidermidis (each with a MIC value of 8 μg/ml), while conidiogenol ( 7 ) showed obvious activity against P. fluorescens and S. epidermidis (each with a MIC value of 16 μg/ml). This is the first report on antimicrobial activity of cyclopiane diterpenes.     

A chemometric interpopulation study of the essential oils of Cistus creticus L. growing in Crete (Greece)

The chemical composition of the essential oils of twenty-five populations of Cistus creticus subsp. creticus L. from the island of Crete (Greece) and their interpopulation variability were analysed in detail by GC-MS. 142 compounds were identified representing an average of 56.8-89.8% of the oil composition. The components are represented here by homologous series of monoterpenes, oxygenated monoterpenes, sesquiterpenes, oxygenated sesquiterpenes, diterpenes, labdane diterpenes, aldehydes, alkanes, esters, fatty acids, ketones, and others. Labdane diterpenes were detected and identified in the essential oils and have been found in high percentage composition. The results from the chemical analysis of the essential oils were submitted to chemometric cluster analysis in order to detect some pattern distribution and to identify which constituents can differentiate the groups of individuals. Two main chemotypes (clusters) were well differentiated; the first deals with eight populations of West Crete and the second with the rest of the populations. Cluster analysis based on labdane type diterpenes patterns, proved to be the best chemotype for the examined populations among the other chemical groups.