Clerodane diterpenes from Aristolochia species

The investigation of Aristolochia brasiliensis and A. esperanzae afforded 12 clerodane derivatives, including the following six novel ones: rel (5S, 8R, 9S, 10R)-2-oxo-ent-3-cleroden-15-oic acid, rel (5S, 8R, 9S, 10R)-2-oxo-ent-clerod-3,13-dien-15-oic acid methyl ester, (5R, 8R, 9S, 10R)-ent-3-cleroden-15-oic acid, rel (5S, 8R, 9S, 10R)-ent-clerod-3,13-dien-15-oic acid, (2S, 5R, 8R, 9S, 10R)-2-hydroperoxy-ent-3-cleroden-15-oic acid methyl ester and (2S, 5R, 8R, 9S, 10R)-2-hydroperoxy-ent-clerod-3,13-dien-15-oic acid methyl ester. The structures were assigned on the basis of spectral data and derivatization by chemical reactions. The occurrence of this type of diterpene has not previously been reported in Aristolochiaceae. © 1987.

Clerodane diterpenes from leaves of Casearia sylvestris swartz

Ethanolic extracts of the leaves of Casearia sylvestris yielded a novel clerodane diterpene, 15-hydroxy-3-cleroden-2-one, together with the known diterpenes (-)-hardwickiic acid, reported for the first time from this species, and casearins B and G, previously isolated from C. sylvestris. The structures of all four compounds were determined by spectrometric analysis. The new clerodane diterpene and (-)-hardwickiic acid contain structural features that are completely different from the highly oxygenated casearins and casearvestrins isolated from C. sylvestris.

Assessment of the chemopreventive effect of casearin B, a clerodane diterpene extracted from Casearia sylvestris (Salicaceae)

Studies have shown that Casearia sylvestris compounds protect DNA from damage both in vitro and in vivo. Complementarily, the aim of the present study was to assess the chemopreventive effect of casearin B (CASB) against DNA damage using the Ames test, the comet assay and the DCFDA antioxidant assay. The genotoxicity was assessed by the comet assay in HepG2 cells. CASB was genotoxic at concentrations higher than 0.30μM when incubated with the FPG (formamidopyrimidine-DNA glycosylase) enzyme. For the antigenotoxicity comet assay, CASB protected the DNA from damage caused by H2O2 in the HepG2 cell line in concentrations above 0.04μM with post-treatment, and above 0.08μM with pre-treatment. CASB was not mutagenic (Ames test) in TA 98 and TA 102. In the antimutagenicity assays, the compound was a strong inhibitor against aflatoxin B1 (AFB) in TA 98 (>88.8%), whereas it was moderate (42.7-59.4%) inhibitor against mytomicin C (MMC) in TA 102. Additionally, in the antioxidant assay using DCFDA, CASB reduced reactive oxygen species (ROS) generated by H2O2. In conclusion, CASB was genotoxic to HepG2 cells at high concentrations; was protective of DNA at low concentrations, as shown by the Ames test and comet assay; and was also antioxidant. © 2012 Elsevier Ltd.

Morphological and biochemical alterations activated by antitumor clerodane diterpenes

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Development of a comprehensive method for analyzing clerodane-type diterpenes and phenolic compounds from Casearia sylvestris Swartz (Salicaceae) based on ultra high performance liquid chromatography combined with chemometric tools

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Pathogen-responsive expression of a putative ATP-binding cassette transporter gene conferring resistance to the diterpenoid sclareol is regulated by multiple defense signaling pathways in arabidopsis

The ATP-binding cassette (ABC) transporters are encoded by large gene families in plants. Although these proteins are potentially involved in a number of diverse plant processes, currently, very little is known about their actual functions. In this paper, through a cDNA microarray screening of anonymous cDNA clones from a subtractive library, we identified an Arabidopsis gene (AtPDR12) putatively encoding a member of the pleiotropic drug resistance (PDR) subfamily of ABC transporters. AtPDR12 displayed distinct induction profiles after inoculation of plants with compatible and incompatible fungal pathogens and treatments with salicylic acid, ethylene, or methyl jasmonate. Analysis of AtPDR12 expression in a number of Arabidopsis defense signaling mutants further revealed that salicylic acid accumulation, NPR1. function, and sensitivity to jasmonates and ethylene were all required for pathogen-responsive expression of AtPDR12. Germination assays using seeds from an AtPDR12 insertion line in the presence of sclareol resulted in lower germination rates and much stronger inhibition of root elongation in the AtPDR12 insertion line than in wild-type plants. These results suggest that AtPDR12 may be functionally related to the previously identified ABC transporters SpTUR2 and NpABC1, which transport sclareol. Our data also point to a potential role for terpenoids in the Arabidopsis defensive armory.

Antimicrobial activity of the extract and isolated compounds from Baccharis dracunculifolia D. C. (Asteraceae)

Baccharis dracunculifolia D. C. (Asteraceae) is the most important plant source of the Brazilian green propolis. Since propolis is known for its antimicrobial activity, the aim of this work was to evaluate the showed that the leaves extract of B. dracunculifolia (BdE) presents antifungal and antibacterial activities, especially against Candida krusei and Cryptococcus neoformans, for which the BdE showed IC50 values of 65 mu g mL(-1) and 40 mu g mL(-1), respectively In comparison to the BdE, it was observed that the green propolis extract (GPE) showed better antimicrobial activity, displaying an IC50 value of 9 mu g mL(-1) against C krusei. Also, a phytochemical study of the BdE was carried out, affording the isolation of ursolic acid (1), 2 alpha-hydroxy-ursolic acid (2), isosakuranetin (3), aromadendrin-4`-methylether (4), baccharin (5), viscidone (6), hautriwaic acid lactone (7), and the clerodane diterpene 8. This is the first time that the presence of compounds 1, 2, and 8 in B. dracunculifolia has been reported. Among the isolated compounds, 1 and 2 showed antibacterial activity against methicillin-resistant Staphylococcus aureus, displaying IC50 values of 65 mu g mL(-1) and 40 mu g mL(-1), respectively. 3 was active against C neoformans, showing an IC50 value of 15 mu g mL(-1) and a MIC value of 40 mu g mL(-1), while compounds 4-8 were inactive against all tested microorganisms. The results showed that the BdE, similar to the GPE, displays antimicrobial activity, which may be related to the effect of several compounds present in the crude extract.

Constituents of glandular trichomes of Tithonia diversifolia: Relationships to herbivory and antifeedant activity

The herbivory activity of the bordered patch larvae (Chlosyne lacinia, Lepidoptera) on leaves of a Brazilian population of Tithonia diversifolia and the antifeedant potential of its leaf rinse extract were investigated. The caterpillars fed only on the adaxial face, where the density of glandular trichomes is very low, and avoided the abaxial face, which contains high levels of trichomes. Deterrent activity against the larvae was observed in leaf discs treated with leaf rinse extract at concentrations of 1-5% of fresh leaf weight. High-performance liquid chromatography (HPLC) analysis indicated that sesquiterpene lactones are the main constituents of the glandular trichomes. Dichloromethane rinse extracts of the leaves and inflorescences were chemically investigated, and 16 compounds were isolated and identified: 14 sesquiterpene lactones, a flavonoid and a diterpenoid. In this study, five sesquiterpene lactones are described for the first time in the genus, including two lactones, one of which has an unusual seco-guaianolide skeleton. Our findings indicate that the caterpillars avoid the sesquiterpene-lactone-rich glandular trichomes, and provide evidence for the antifeedant activity of the dichloromethane leaf rinse extract. In addition, a study of the seasonal variation of the main constituents from the leaf surface throughout a year demonstrated that a very low qualitative but a very high quantitative variation occurs. The highest level of the main metabolite tagitinin C was observed between September and October and the lowest was from March to June, the later corresponding to the period of highest infestation by the larvae. (C) 2008 Elsevier Ltd. All rights reserved.

Would Sacaca, Croton cajucara Benth (Euphorbiaceae) be an hepatotoxic plant like Germander, Teucrium chamaedrys L. (Labiatae)?

Clinical and experimental studies have consistently incriminated the medicinal plant germander (Teucrium chamaedrys L.) in epidemic and sporadic cases of liver diseases. The sacaca (Croton cajucara Benth), a common plant in Brazilian Amazon region also comes being incriminated in similar clinical cases. Of both plants were isolated diterpenoid coumpounds with similar chemical structures.

Salvia divinorum: an hallucinogenic mint which might become a new recreational drug in Switzerland.

Salvia divinorum Epling & Jativa is an hallucinogenic mint traditionally used for curing and divination by the Mazatec Indians of Oaxaca, Mexico. Young people from Mexican cities were reported to smoke dried leaves of S. divinorum as a marijuana substitute. Recently, two S. divinorum specimens were seized in a large-scale illicit in-door and out-door hemp plantation. Salvinorin A also called divinorin A, a trans-neoclerodane diterpene, was identified in several organic solvent extracts by gas chromatography-mass spectrometry. The botanical identity of the plant was confirmed by comparing it to an authentic herbarium specimen. More plants were then discovered in Swiss horticulturists greenhouses. All these data taken together suggest that many attempts exist in Switzerland to use S. divinorum as a recreational drug. This phenomenon may be enhanced because neither the magic mint, nor its active compound are banned substances listed in the Swiss narcotic law.

Bioactive glycosides from Chinese medicines

Glycosides are the bioactive components of many famous Chinese medicines. Here reported are some bioactive glycosides we discovered from Chinese medicines in recent years. (1) Pheolic glycosides from Chinese medicines: Gastrodia elata, acontium austroynanense and Helicia erratica, three bioactive phenolic glycosides were discovered and two of them have been developed into new drugs. (2) Terpenoidal glycosides: a) Monoterpenoid: the sweroside from Swertia mollensis has been developed intro an anti-hepatitis drug; b) Diterpenoid: Phlomis betonicoides contains sweet glycoides; c) Triterpenoid: many biologically active triterpenoid glycosides were isolated from Panax plants and Siraitia grosvenorii. (3) Steroidal glycosides: a) C21-steroid: Cynanchum otophyllum and C. atratrum contain anti-epilepsy and-tumor glycosides; b) C27-steroid Hemostatic saponins were found in Paris polyphylla.

Determinação da Estereoquímica Relativa de Pimaradienos Através de Produtos de Oxidação

Pimaradienes, including isopimaradienes, with an endocyclic double bond between C-9 and C-11 are uncommon compounds in nature. The diterpenoid pimar-9(11),15-dien-19-oic acid (1) was isolated from Mikania triangularis (Asteraceae) and the correct stereochemistry of 1was established by ¹H and 13C NMR studies of several oxidative products, mainly epoxides, of this compound and its double bond isomers.

Ácido ent-16alfa,17-diidroxicauran-19-óico isolado de Ouratea semiserrata e os desafios estereoquímicos dos carbonos quirais C-4 e C-16

Phytochemical investigation of the leaves and branches of a specimen of Ouratea semiserrata led to the isolation and characterization of ent-16alpha,17-dihydroxykauran-19-oic acid, along with other natural products. This diterpenoid and its derivatives were used to unambiguous ¹H and 13C chemical shifts assignments and to indicate some mistake data described in the literature as consequence mainly of the stereochemicals of the chiral carbons C-4 and C-16. The HRMS spectra were also analysed.

Gênero Baccharis (Asteraceae): aspectos químicos, econômicos e biológicos

The Baccharis genus is represented by more than 500 species distributed mainly in the tropical areas of South America. Many of them are extensively used in folk medicine in the treatment or prevention of anemias, inflammations, diabetes and stomach, liver and prostate diseases. Phytochemical and biological investigations in about 120 species resulted mainly in the isolation of clerodane and labdane diterpenes and flavonoid aglicones with the flavone unit being the most frequent.