Isolation and structure of antipeptic ulcer diterpene from Thai medicinal plant.

Ogiso, Akira; Kitazawa, Eiichi; Kurabayashi, Masaaki; Sato, Ayato; Takahashi, Shuji; Noguchi, Hiroshi; Kuwano, Harumitsu; Kobayashi, Shinsaku; Mishima, Hiroshi

doi:10.1248/cpb.26.3117

Cited by 84 publications

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“…In C. sublyratus, an electron microscope study by De-Eknamkul and Potduang 28) showed that the main diterpene, plaunotol (18-hydroxy geranylgeraniol) 29) was accumulated in the leaf chloroplasts (Fig. 4), suggesting that the plaunotol biosynthesis is catalyzed by the enzymes present in chloroplasts.…”

Section: )mentioning

confidence: 99%

Geranylgeranyl Diphosphate Synthase from Scoparia dulcis and Croton sublyratus. Plastid Localization and Conversion to a Farnesyl Diphosphate Synthase by Mutagenesis.

Sitthithaworn

Kojima

Viroonchatapan

et al. 2001

CHEMICAL & PHARMACEUTICAL BULLETIN

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Geranylgeranyl diphosphate synthase (GGPPS), a member of the short-chain isoprenyl diphosphate synthase family, catalyzes the consecutive condensation of three molecules of isopentenyl diphosphate (IPP) with dimethylallyl diphosphate (DMAPP) to give a C 20 compound which is a precursor to diterpenes, carotenoids and chlorophylls.1,2) Meanwhile, farnesyl diphosphate synthase (FPPS) produces a C 15 compound which is utilized as a precursor in the biosynthesis of sesquiterpenes, steroids and farnesylated proteins, and geranyl diphosphate synthase (GPPS) produces geranyl diphosphate (C 10 ), the key precursor of monoterpene biosynthesis. 3)Genes encoding GPPS, FPPS and GGPPS have been isolated from various organisms. Sequence comparison of these enzymes revealed several conserved regions including two aspartate-rich DDXX(XX)D motifs. [4][5][6] X-ray crystallography study of an avian FPPS revealed that these two aspartate rich-motifs, which are located on opposite walls of a large central active-site cavity, act as binding sites for the metal ions that form complexes with the diphosphate moieties of the two substrates.7) Site-directed mutagenesis and crystallographic studies also indicated that the amino acids in the region around the first aspartate-rich motif (FARM) are essential in determining the ultimate length of the product polyisoprenoid chain. Hence, replacement of Phe-112 and Phe-113, situated at the fifth and fourth amino acid upstream to FARM in the avian FPPS, with smaller side chain amino acids gave FPPS mutants that synthesized longer polyisoprenoid products than FPP.8) Further, in both cases of bacillus FPPS 9) and archaeal GGPPS, 10) replacements of the aromatic amino acid situated at the fifth amino acid before FARM to a non-aromatic amino acid caused a change of the product specificity. The mutant enzymes were able to catalyze consecutive condensations beyond the destined limit of the original enzymes, and the chain lengths of their final products were dependent on the bulk of the side chain of the substituted amino acid.11) On the basis of these mutation studies, 12) it was proposed that the mechanism of the product length determination in eukaryotic FPPS is different from those of prokaryotic FPPS. In eukaryotic FPPS, both of the aromatic amino acids at the fourth and fifth positions before FARM directly block the chain elongation greater than C 15 and provide product specificity. In contrast, the product specificity of prokaryotic FPPS is determined by an aromatic amino acid at the fifth position before FARM and two amino acids inserted in FARM.Few studies, however, have been reported concerning what structural factor(s) determines the product chain length in plant GGPPSs. To this end, GGPPSs from two diterpene-producing plants, Scoparia dulcis and Croton sublyratus, were cloned, functionally expressed in Escherichia coli, 13) and the mutants were analyzed for product specificity. A comparison of amino acids around the FARMs of FPPSs and GGPPSs of plant origin revealed two distinctive points. Fi...

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Section: )mentioning

confidence: 99%

Geranylgeranyl Diphosphate Synthase from Scoparia dulcis and Croton sublyratus. Plastid Localization and Conversion to a Farnesyl Diphosphate Synthase by Mutagenesis.

Sitthithaworn

Kojima

Viroonchatapan

et al. 2001

CHEMICAL & PHARMACEUTICAL BULLETIN

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“…The structure of the compound was proved to be the diterpene by spectroscopic method and synthesis (19). The compound was proved to be a potent antipeptic ulcer drug and it is now commercially available under the trade name of Kelnec.…”

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confidence: 99%

Bioactive natural products from Thai plants

Mahidol¹,

Sahakitpichan²,

Ruchirawat³

1994

Pure and Applied Chemistry

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Abstract.The investigation of Thai medicinal plants for the potential therapeutic agents is surveyed with a particular emphasis on the search for antimalarial agents. The study on Diospyros mollis, Croton sublyratus, and Phyllanthus amarus is described.Thailand is uniquely located to represent the fauna and flora which characterizes the biogeographic province of Indo-Burma. A number of the eastern Himalaya temperate taxa penetrate south into the northern mountains of Thailand while the southern part is evergreen forest thus making this area one of the richest floristic regions of the world (1). It has been estimated that the vascular plants in Thailand are not less than 10,000 species of about 1,763 genera from 245 families (2). The numbers of alkaloidcontaining plants are estimated to be only about 266 species of 176 genera in 67 families based on the Thai plants names and parts of the uncompleted flora of Thailand (3).The potential of natural products as therapeutic agents in the treatment of malaria is enormous. Quinine was introduced as an antimalaiial for more than a century ago. Quinine also served as a prototype as an antimalarial leading to the discovery of synthetic antimalarials based on the quinoline compounds. 4-and 8-Aminoquinoline derivatives have proved their efficacy as antimalarials. Mefloquine, a quinoline methanol derivative, has recently been introduced as an antimalarial.The Chinese has a long history of use of a herb called Qing hao (Artemisia annua) for the treatment of malaria. The pure compound was isolated in 1972 and named Qinghaosu (QHS) or Arteannuin meaning the "active principle of Qing hao"(4) In Thailand, interests for the use of herbal medicine for the treatment of malaria has been long standing. Lately many groups of Thai scientists have been working on various plants to scrutinize the validity of these 'claims' as well as searches for new antimalarial agents from plants. During the second world war, Professor Ketusingh attempted to use 30 herbal medicine to treat malaria. The treatments were applied to 543 patients with infections with P. falciparum (255 patients) and P. vivax. (288 patients)(5). From the study the plant of Oroxylum indicum showed the total cure rate as high as 65.7% and it is very interesting to note the definite prefeicnce for the plants of Azadirachta and Nyctanthes arbor-tritis for the treatment of those patients infected with P. vivaxScientists at Division of Medical Research, Department of Medical Sciences, Ministry of Public Health and at AFRIMS (Aimed Force Research Institute for Medical Science) have been interested in the search for antimalarial agents from Thai medicinal plants (6).After screening many plants, the four plants (Brucea javanica, Picrasma javanica, Celastrus paniculatus, and Tiliacora triandra ) which exhibited the minimal inhibitory concentration (MIC) of not more than 25 microgram per millilitre were then further studied by extraction with various solvents, each solvent extract was then again tested. The chloroform extracts gave the b...

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“…Because of the discovery of stellate-dendritic trichome, the name has been changed to C. stellatopilosus Ohba (Esser and Chamarit, 2001). Diterpenelactones, furanoid diterpenes, diterpene alcohols such as plaunotol (18-hydroxygeranylgeraniol), ent-13α-hydroxy-13-epimanol, ent-16 -,17-dihydroxykaurane and an ester of 18-hydroxygeranylgeraniol have been reported from C. stellatopilosus (Ogiso et al, 1978;Kitazawa et al, 1979Kitazawa et al, , 1980Kitazawa et al, , 1982Kitazawa and Ogiso, 1981;Takahashi et al, 1983). Among these compounds, plaunotol is a pharmacologically active component responsible for the eradication of Helicobacter pylori, which is highly associated with gastritis and peptic ulcers and accelerates ulcer healing effects (Ogiso et al, 1985;Koga et al, 0939Ð5075/2007/0500Ð0389 $ 06.00 " 2007 Verlag der Zeitschrift für Naturforschung, Tübingen · http://www.znaturforsch.com · D 2002).…”

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confidence: 99%

Establishment of Croton stellatopilosus Suspension Culture for Geranylgeraniol Production and Diterpenoid Biosynthesis

Wungsintaweekul

Tewtrakul²,

Kongduang³

et al. 2007

Zeitschrift Für Naturforschung C

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Diterpenoids in higher plants are biosynthesized from isoprene units obtained from two distinct pathways: the mevalonate pathway and the deoxyxylulose phosphate pathway. The metabolic partitioning of both pathways in plant species is dependent upon the type of culture. In order to study the diterpenoid biosynthesis in Croton stellatopilosus cell culture, callus culture was firstly induced from C. stellatopilosus young leaves in Murashige and Skoog (MS) medium in the presence of 1.0 mg/l 2,4-dichlorophenoxyacetic acid (2,4-D), 1.0 mg/l benzyladenine (BA), 3% (w/v) sucrose and 0.8% (w/v) agar. The suspension culture was further induced from its callus in the same medium without gelling agent. Detection of diterpenoid accumulation by gas chromatography-mass spectrometry revealed that a cell culture could accumulate a low amount of geranylgeraniol (GGOH) and a high content of fatty acids and phytosterols. To improve the GGOH production, the culture conditions were optimized by medium manipulation in terms of hormonal factors. The growth rates of cell cultures were similar in all kinds of media. The GGOH production curve indicated that GGOH plays an important role as a primary metabolite in the cell culture. The optimum medium for GGOH production was MS medium supplemented with 2.0 mg/l 2,4-D and 2 mg/l BA that could produce GGOH with a yield of 1.14 mg/g FW.

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Isolation and structure of antipeptic ulcer diterpene from Thai medicinal plant.

Cited by 84 publications

References 0 publications

Geranylgeranyl Diphosphate Synthase from Scoparia dulcis and Croton sublyratus. Plastid Localization and Conversion to a Farnesyl Diphosphate Synthase by Mutagenesis.

Geranylgeranyl Diphosphate Synthase from Scoparia dulcis and Croton sublyratus. Plastid Localization and Conversion to a Farnesyl Diphosphate Synthase by Mutagenesis.

Bioactive natural products from Thai plants

Establishment of Croton stellatopilosus Suspension Culture for Geranylgeraniol Production and Diterpenoid Biosynthesis

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