Studies on bioactive components from Chinese medicinal plants

Several novel bioactive components isolated from Chinese medicinal plants will be presented. These include novel maytansinoid tumor, inhibitors, some new ent-kaurane and rosane diterpenoids from Mallotus anomalus Meer et Chun (Euphorbiaceae), as well asnovel insecticide, stemona alkaloids from Stemona parviflora C. H. Wright (Stemonaceae). Both are native plants of Hainan island, Chine. 2D NMR techniques such as mono and hetero-COSY, NOESY, COLOC as well as H-NMR line broadening effect were utilized for structure elucidation. The separation techniques, struture elucidations and bioassay results will be reported.

Investigation phytochimique d'une plante médicinale malgache Hypoestes serpens (Vahl) R. Br. (Acanthaceae) variété glabre et étude comparative avec la variété poilue

Résumé A Madagascar, comme dans plusieurs pays en développement, une grande partie de la population utilise les plantes pour se soigner. Plusieurs espèces des plantes sont ainsi utilisées en médecine traditionnelle malgache. Par ailleurs, la plupart de ces plantes ne font l'objet que de très peu d'étude scientifique. En effet, dans le cadre de l'investigation phytochimique de plantes utilisées en médecine traditionnelle malgache et dans la recherche des nouvelles substances biologiquement actives, Hypoestes serpens (Vahl) R. Br. (Acanthaceae) a été étudiée. Elle se présente sous deux variétés (glabre et poilue) qui sont tous utilisées dans la région sud-centre de Madagascar pour traiter la blennorragie. De l'extrait dichlorométhanique des feuilles de H. serpens (Vahl) R. Br. variété glabre, 12 diterpénoides dont 8 nouveaux ont été isolés. Ils ont tous montré une activité antifongique contre un champignon pathogène des plantes, Cladosporium cucumerinum, dans la bioautographie directe sur CCM. Quelques-uns ont également présenté une activité contre une levure saprophyte chez l'homme, Candida albicans et une activité inhibitrice de l'enzyme acétylcholinesterase. Les diterpènoïdes sont déjà considérés comme les principaux métabolites secondaires du genre Hypoestes. Le fractionnement de l'extrait méthanolique a conduit à l'isolement de 5 glycosides des flavonoïdes dont 4 sous formes C-g,lycosides qui n'ont jamais été identifiés dans la famille Acanthaceae. Ces flavonoïdes ont présenté une activité antiradicalaire contre le DPPH. Le fractionnement et la purification des extraits ont été effectués à l'aide des différentes techniques chromatographiques telles que la chromatographie sur colonne ouverte, la filtration sur gel, la chromatographie liquide à haute pression, la chromatographie liquide à moyenne pression et la chromatographie liquide à basse pression. Par ailleurs, les structures des composés isolés ont été élucidées par des techniques spectroscopiques (UV, MS, RMN) et de méthode chimique (hydrolyse acide). En plus de ces techniques, certaines méthodes physiques (cristallographie par rayons-X, mesure de rotation optique) ont été réalisées pour confirmer certaines structures. Comme l'espèce Hypoestes serpens (Vahl) R. Br. se présente en deux variétés, une étude comparative a été effectuée. Cette étude avait montré que ces deux variétés ont une activité biologique similaire. Finalement, une technique analytique couplée, HPLC-UV-APC1-MS a permis de montrer la présence de toutes les substances isolées de la variété glabre dans la variété poilue. Second résumé Depuis des milliers d'almées, l'homme utilise les plantes pour se soigner. De nos jours, même avec le développement de la médecine moderne, la phytothérapie reste toujours la forme des soins de santé abordable et accessible pour la majorité des populations rurales des pays en développement. En outre, les plantes médicinales constituent une source potentielle de molécules biologiquement actives pour les industries pharmaceutiques et actuellement, on estime que 25% des médicaments commercialisés dans le monde sont à base de plantes Dans le cadre de la recherche des nouvelles molécules à intérêt thérapeutique qui pourraient devenir un médicament ou un modèle de structure ("lead compound") pour le développement de nouveaux médicaments, nous avons fait une étude sur l'espèce, Hypoestes serpens (Vahl) R. Br, plante utilisée en médecine traditionnelle malgache. Cette espèce existe en deux variétés, une glabre et une autre poilue qui sont tous utilisées dans la région sud-centre de Madagascar pour traiter la blennorragie. Par ailleurs, les tradipraticiens utilisent de préférence la variété poilue. Dans la première partie de ce présent travail, une investigation phytochimique de H serpens, variété glabre (variété moins utilisée) a d'abord été effectuée afm d'isoler et d'identifier le maximum des molécules biologiquement actives qu'elle contient. De ce fait, 17 composés dont 8 nouveaux ont été isolés. Les potentiels d'activités thérapeutiques des substances isolées ont ensuite été dépistés sur les différents cibles suivants.: deux souches de champignons (Cladosporium cucumerinum et Candida albicans), l'enzyme acétylcholinesterase et le radical DPPH. La deuxième partie de ce travail a été consacrée sur l'étude comparative des deux variétés (glabre et poilue) de H. serpens à la fois sur le plan biologique et sur le plan phytochimique. A l'issue de cette comparaison, nous avons constaté que l'utilisation de ces deux variétés en médecine traditionnelle malgache n'est pas un hasard ; les deux variétés avaient présenté une activité biologique très remarquable et contiennent les mêmes substances actives. Ces résultats démontrent les potentiels thérapeutiques de H serpens en médecine traditionnelle malgache et pourraient également encourager les tradipraticiens à utiliser la variété glabre tout en protégeant la variété poilue qui est en voie de disparition actuellement. En bref, l'investigation phytochimique de H. serpens justifiée par l'isolement et l'identification de certains de ses principes actifs ouvre la voie aux recherches des médicaments d'origine naturelle. Abstract In Madagascar, as in many developing countries, most people use plants to cure. A large number of plant species are employed in Malagasy traditional medicine. Moreover, most of these plants have been subject only very little scientific study. As part of a phytochemical investigation of plants used in Malagasy traditional medicine and in the search for new biologically active substances, Hypoestes serpens (Vah1) R.Br. (Acanthaceae) was investigated. This species exists in two varieties (glabrous and hairy) which are used in the south-center part of Madagascar to treat gonorrhoea. From the dichloromethane extract of the leaves of H. serpens (Vah1) R. Br. glabrous variety, 12 diterpenoids 8 of which were new, were isolated. They showed antifungal activity against the plant pathogen Cladosporium cucumerinum, in the direct TLC bioautography. Some of them also had activity against the yeast Candida athicans and inhibited acetylcholinesterase. The diterpenes are considered as the principal secondary metabolites of the genus Hypoestes. Fractionation of the methanol extract led to the isolation of 5 flavonoid glycosides, 4 of which were C-glycosides, never before identified in the Acanthaceae family. These flavonoids showed radical scavenging activity against DPPH. The fractionation and the purification of the extracts were achieved by different chromatographic techniques such as open-column chromatography, gel filtration, high- pressure liquid chromatography, medium-pressure liquid chromatography and low-pressure liquid chromatography. Moreover, the structures of the isolated compounds were elucidated by spectroscopic techniques (UV, MS, NMR) and chemical technique (acid hydrolysis). In addition, some physical methods (X-ray crystallography, measurement of optical rotation) were performed to confirm some structures. As the species Hypoestes serpens (Vah1) R. Br. is present in two varieties, a comparative study was carried out. This study showed that these two varieties had similar biological activity. Finally, a coupled analytical technique HPLC-UV-APCI-MS showed the presence of the same compounds in both the glabrous and hairy varieties.

Mono and diterpenes from seeds of Xylopia sericea

A monoterpene, 3beta,6beta-dihydroxy-p-menth-1-ene has been isolated from the seeds of Xylopia sericea along with four kaurane, one beyerene, one atisene and four trachylobane diterpenoids, including the trachyloban-18- and 19-methyl esters. The X-ray crystal structure of methyl ent-trachyloban-18-oate was determined in order to make an unambiguous distinction between the 18- and 19-esters. The 13C NMR data for ent-15alpha-hydroxy-trachyloban-19-oic acid has been revised.

Diterpenóides com esqueleto cleistantano de Vellozia aff. carunculares martius ex seubert (Velloziaceae)

From the hexane extract of leaves, stem and roots, of Vellozia aff. carunculares, fourteen cleistanthane diterpenoids were detected by HRGC-MS, through the analysis of their fragmentation patterns. Comparison of their MS spectra with those of authentic standards previously isolated from other species of the family Velloziaceae allowed the identification, with a high degree of confidence, of eigth known cleistanthane diterpenoids. Of these, four were isolated and identified from their MS, IR and ¹H and 13C NMR spectra, as the known cleistantha-8,11,13-trien-7-one, cleistantha-8,11,13-trien-3,7-dione, cleistantha-1,8,11,13-tetraen-3,7-dione and the first reported 6-alpha-hydroxy-cleistantha-8,11,13-trien-7-one. The triterpenoid beta-amyrin was also isolated.

Diterpenos tipo abietano isolados de Plectranthus barbatus Andrews

Plectranthus barbatus is largely used in the Northeast region of Brazil by the local population for treatment of digestive problems as substitute of boldo (Pneumus boldus). Phytochemical analysis of the leaf extracts of Plectranthus barbatus (Labiatae) cultivated in this region yielded two abietane diterpenoids, cyclobubatusin (1) and barbatusin (2) and a new one named 7beta-acetyl-12-deacetoxycyclobutatusin (3). The structures of the isolated compounds were established by spectral analysis, using mainly mass spectra and ¹H and 13CNMR (1D and 2D). These procedures permitted the assignment of all chemical shifts in the diterpenoids.

Diterpenos casbanos e acetofenonas de Croton nepetaefolius (Euphorbiaceae)

Croton nepetaefolius is an aromatic plant native to the northeast of Brazil where it is extensively used in folk medicine as a sedative, orexigen and antispasmodic agent. The present work deals with the chromatographic analysis of the ethanolic extract of Croton nepetaefolius stalk. It allowed the isolation and characterization of two diterpenoids named 1,4-dihydroxy-2E,6E,12E-trien-5-one-casbane and 4-hydroxy-2E,6E,12E-5-one-casbane, two acetophenones named 2-hydroxy-4,6-dimethoxyacetophenone and 2-hydroxy-3,4,6-trimethoxyacetophenone and the steroids 3-O-b-D-glucopiranosylsitosterol and a mixture of b-sitosterol and stigmasterol. Structural elucidation was done on the basis of spectral data, mainly high field NMR and EIMS.

Composição molecular e origem paleobotânica de âmbares da bacia do Araripe, Formação Santana

The terpenoid composition of seven amber samples from Araripe Basin (Santana Formation, Crato Member) has been analyzed by gas chromatography-mass spectrometry to determine their botanical origin. The diterpenoids, which have been identified in the fossil resin extracts are derived primarily from the abietane class, e.g., dehydroabietane, 4-epidehydroabietol, 16,17,18-trisnorabieta-8,11,13-triene, 7-oxo-16,17,19-trisnorabieta-8,11,13-trieno, dehydroabietic acid, ferruginol, hinokiol and hinokione. Their composition is certainly typical for conifers, and angiosperms can be excluded as the botanical source, as no triterpene was identified. The terpenoid characteristics strongly support a relationship to the Araucariaceae or Podocarpaceae families. In addition, the fossil record of the embedding sediments (pollen and fossil leaves) also supports the proposal of these paleobotanical origins for the ambers.

Avaliação de diterpenos isolados de P. ornatus como potenciais inibidores da COX-1

Os produtos naturais são uma importante fonte de possíveis novos fármacos para uso clínico. O Plectranthus ornatus Codd. pertence a um género associado ao isolamento de diterpenos que são compostos responsáveis ??por diversas actividades biológicas. Os três diterpenos em estudo foram isolados no passado de P. ornatus e são agora avaliados como potenciais inibidores da COX-1. Os resultados obtidos sugerem que o ácido rinocerotinoico (2), mas não a plectrornatina C (1) e o halimano (3), apresenta uma ligeira actividade inibidora da COX-1. Estudos em desenvolvimento visam entender se estes compostos têm efeito como inibidores da COX-2. Deste modo, pretendese verificar o seu possível interesse como agentes anti-inflamatórios.

New alkamide and ent-kaurane diterpenoid derivatives from Senecio erechtitoides (Asteraceae)

Fractionation of a MeOH/CH2Cl2 (1/1) extract of the aerial parts of Senecio erechtitoides led to the isolation of six compounds including the hitherto unknown N-phenethylamide derivative named N-(p-hydroxyphenethyl)pentacosanamide (1), and a kauranoid derivative named derivative named ent-7-oxo-16 alpha,17-dihydroxykauran-19-oic acid (2), as well as four known compounds, ent-Kaur-16-en-19-oic acid (3), ent-7 beta-hydroxykaur-16-en-19-oic acid (4), ent-7-oxokaur-16-en-19-oic acid (5), steppogenin 4′-O-beta-d-glucoside (6). Their structures and relative configurations were elucidated on the basis of spectroscopic methods, chemical reactions, and comparison with previously known analogs. All isolates were evaluated for their antimicrobial activity and only diterpenoids were found to possess a potent inhibitor effect against the range of microorganism.

Actions of octocoral and tobacco cembranoids on nicotinic receptors

Nicotinic acetylcholine receptors (AChRs) are pentameric proteins that form agonist-gated cation channels through the plasma membrane. AChR agonists and antagonists are potential candidates for the treatment of neurodegenerative diseases. Cembranoids are naturally occurring diterpenoids that contain a 14-carbon ring. These diterpenoids interact with AChRs in complex ways: as irreversible inhibitors at the agonist sites, as noncompetitive inhibitors, or as positive modulators, but no cembranoid was ever shown to have agonistic activity on AChRs. The cembranoid eupalmerin acetate displays positive modulation of agonist-induced currents in the muscle-type AChR and in the related gamma-aminobutyric acid (GABA) type A receptor. Moreover, cembranoids display important biological effects, many of them mediated by nicotinic receptors. Cembranoids from tobacco are neuroprotective through a nicotinic anti-apoptotic mechanism preventing excitotoxic neuronal death which in part could result from anti-inflammatory properties of cembranoids. Moreover, tobacco cembranoids also have anti-inflammatory properties which could enhance their neuroprotective properties. Cembranoids from tobacco affect nicotine-related behavior: they increase the transient initial ataxia caused by first nicotine injection into naive rats and inhibit the expression of locomotor sensitization to repeated injections of nicotine. In addition, cembranoids are known to act as anti-tumor compounds. In conclusion, cembranoids provide a promising source of lead drugs for many clinical areas, including neuroprotection, smoking-cessation, and anti-cancer therapies. (C) 2009 Elsevier Ltd. All rights reserved.

PHENYLBUTANOID AND TAXANE-LIKE METABOLITES FROM NEEDLES OF TAXUS-BREVIFOLIA

The structures for brevifoliol and three baccatin VI derivatives were revised to possess the novel 11(15 --> 1)-abeotaxane tricylic skeleton based on X-ray crystallographic studies. Four more new rearranged taxane derivatives related to brevifoliol and the unusual phenylbutanoid, (-)-rhododendrol, were isolated from the needles of Taxus breuifolia. Their structures were established as 10 beta-benzoxy-5 alpha-(3'-dimethylamino-3'-phenyl)-propanoxy-1 beta-hydroxy- 7 beta,9 alpha,13 alpha-triacetoxy-11(15 --> 1)-abeotaxa-4(20),11-diene; 10 beta-benzoxy-1 beta-hydroxy-5 alpha-(3'-methylamino-3'-phenyl)- propanoxy-7 beta,9 alpha,l3 alpha-triacetoxy-11(15 --> 1)-abeotaxa-4(20),11-diene; 10 beta-benzoxy-5 alpha-cinnamoxy-1 beta-hydroxy-7 beta,9 alpha,13 alpha-triacetoxy-1 1(15 --> 1)-abeotaxa-4(20),11-diene; 10 beta-benzoxy-1 beta,5 alpha-dihydroxy-7 beta,9 alpha,13 alpha-triacetoxy-11(15 --> 1)-abeotaxa-4(20),11-diene and 2(R)-hydroxy-4-(4'-hydroxyphenyl)-butane.

A general survey and some taxonomic implications of diterpenes in the Asteraceae

This paper provides a general survey of the occurrence of diterpenes in the Asteraceae. Data on 4351 botanical occurrences were obtained from the literature. These were grouped by skeleton for each genus. Then, the genera were grouped by subtribes, which, in turn, were gathered in tribes, followed by subfamilies. In spite of the low number of species containing diterpenes, it was possible to describe some structural features of these compounds, i.e. The skeletal types in various taxa and the positions in some skeletons that are always oxidized or never undergo oxidation in some genera. Thus, it was verified that: in the subfamily Cichorioideae, only a few of the studied species possess diterpenes, wherein kaurane is the most frequent diterpene skeleton. In the Asteroideae, the presence of diterpenes is much greater than that in the Cichorioideae and Carduoideae. At tribal taxonomic level, for example, the Astereae produce labdanes and clerodanes; Heliantheae and Eupatorieae produce kauranes and labdanes, respectively; and Calenduleae produce pimaranes. Some taxonomic implications are presented. (c) 2005 the Linnean Society of London.

Diterpenes from Guarea Trichilioides

Chemical investigation of the leaves of Guarea trichilioides afforded six diterpenoids, including four labdane and two clerodane derivatives. The following four are new: 3-oxolabd-8(17),12Z,14-triene, 3α-hydroxylabd-8(17),12Z,14-triene, 3β-hydroxylabd-8(17),12Z,14-triene and(-)-2-oxo-13-hydroxy,3,14-clerodandiene. Copyright © 1996 Elsevier Science Ltd. All rights reserved.

Chrysobalanaceae: Secondary metabolites, ethnopharmacology and pharmacological potential

Many Chrysobalanaceae species, in special Licania and Parinari, are widely used in folk medicine to treat several diseases. This review describes some aspects of their ethnopharmacology potential, biological activities and the secondary metabolites reported so far for Chrysobalanaceae. The chemical constituents of this family include triterpenoids, diterpenoids, steroids and phenylpropanoids like flavonoids as well as chromones derivatives. © 2012 Springer Science+Business Media Dordrecht.

Genus Xylopia (Annonaceae): Chemical and Biological Aspects

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