Costunolide and Dehydrocostus Lactone as Inhibitors of Killing Function of Cytotoxic T Lymphocytes

Taniguchi, Masatoshi; Kataoka, Takao; Suzuki, Haruo; Uramoto, Masakazu; Andô, Masataka; Arao, Kei; Magae, Junji; Nishimura, Toshio; Ōtake, Noboru; Nagai, Kazuo

doi:10.1271/bbb.59.2064

Cited by 85 publications

(59 citation statements)

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“…11, 3.3 g), among which fractions 2, 3, 5, 6, and 8 showed trypanocidal activity at 25 mg/ml. Fractions 3, 5, and 6 were separately purified by silica gel column chromatography to give compounds 1 (dehydrocostus lactone, 83 mg), 9) Photo-oxidation and Reduction of d-Limonene A stirred solution of d-limonene (2 g) and Rose Bengal (29 mg) in MeOH (29 ml) was irradiated by a high pressure mercury lamp (Riko Kagaku, UV-100HA) under oxygen atmosphere at 0°C for 8.5 h. The mixture was concentrated to dryness, and the residue was dissolved in ether (30 ml) and treated with PPh 3 (2.6 g) at room temperature for 1 h. The mixture was concentrated to dryness and the residue was fractionated by repeated silica gel column chromatography with hexane-AcOEt .0 (C-5), 28.9 (C-7), 36.1 (C-6), 42.5 (C-4), 68.6 (C-1), 110.9 (C-9), 130.8 (C-3), 134.5 (C-2), 147.2 (C-8).…”

Section: Methodsmentioning

confidence: 99%

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Trypanocidal Terpenoids from Laurus nobilis L.

et al. 2002

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Trypanosoma cruzi, a parasitic protozoan of Zoomastigophoria, is the etiologic agent of Chagas' disease which is endemic in Central and South America.1) In our screening work on medicinal plants used in Asian counties for trypanocidal activity, extracts of the dried leaves of Laurus nobilis L. (Lauraceae) showed strong trypanocidal activity against epimastigotes of T. cruzi. Leaves of L. nobilis are used as a spice known as laurel or bay leaf. They are also used as a folk medicine for rheumatism and scabies.2) Although some biological activities such as inhibition of elevation of blood ethanol level in ethanol-loaded rat, 3) inhibition of nitric oxide production in lipopolysaccharide-activated mouse peritoneal macrophages, 4) induction of glutathione Stransferase activity, 5) and nematocidal activity 6) were reported for the constituents of L. nobilis, nothing has been reported on anti-protozoan constituents of this plant. Here, we report the isolation and identification of trypanocidal constituents of L. nobilis. Results and DiscussionDried leaves of Laurus nobilis were successively extracted with hexane, CHCl 3 and MeOH, and each extract was tested for anti-trypanosomal effect by the HeLa cell infection assay.7) As the CHCl 3 and MeOH extracts inhibited infection and proliferation of T. cruzi, and the MeOH extract formed the major part of the extracts, the MeOH extract was further fractionated under the guidance of in vitro trypanocidal activity against epimastigotes of T. cruzi.8) The MeOH extract was suspended in aqueous MeOH and fractionated into hexane soluble, AcOEt soluble, and water soluble fractions. Since the AcOEt soluble fraction showed the strongest activity, it was fractionated by silica gel column chromatography to give three trypanocidal compounds (1-3). These compounds were also isolated from the CHCl 3 extracts.Compounds 1 and 2 were obtained as colorless needles from hexane, mp 58-60°C, and as a colorless oil, respectively. The 1 H-and 13 C-NMR spectra indicated that both compounds were guaiane-type sesquiterpene with three exocyclic methylene moieties. Based on comparisons of the spectral data with those reported, compounds 1 and 2 were identified with dehydrocostus lactone (1) 9) and zaluzanin D (2), 10) H-detected heteronuclear multiple quantum coherence (HMQC) and heteronuclear multiple bond connectivity (HMBC) spectra (Fig. 1) revealed the structure to be 1-hydroperoxy-pmenthan-2-en-8-ol acetate. Treatment of 3 with PPh 3 gave an acetoxy alcohol 4, which showed oxygen-bearing carbons at d C 67.0 (C-1) and d C 84.4 (C-8). This confirmed that 3 had a hydroperoxy and an acetoxy group at positions 1 and 8, respectively. Since nuclear Overhauser effect (NOE) experiments did not provide conclusive stereochemical information, the stereochemistry of 3 was determined by chemical correlations. Photo C-NMR spectra of 7 were identical with those of the diol 8, which was derived from 3 by alkaline hydrolysis followed by reduction with PPh 3 . 12)This result established that the relative stereochemi...

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Section: Methodsmentioning

confidence: 99%

“…Based on comparisons of the spectral data with those reported, compounds 1 and 2 were identified with dehydrocostus lactone (1) 9) and zaluzanin D (2), 10) respectively. Compound 3 was obtained as colorless needles from petroleum ether, mp 87.5-88.5°C.…”

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confidence: 95%

Trypanocidal Terpenoids from Laurus nobilis L.

et al. 2002

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“…It was also found to exhibit an inhibition upon the proliferation of human tumor cell cultures, i.e., A549 (non small cell lung), SK-OV-3 (ovary), SK-MEL-2 (melanoma), XF498 (central nerve system) and , in vitro . Costunolide (1) also inhibits the killing activity of cytotoxic T lymphocytes through preventing the increase in tyrosine phosphorylation in response to the crosslinking of T-cell receptors (Taniguchi et al, 1995).…”

Section: Antitumor and Cytotoxicmentioning

confidence: 99%

Sesquiterpenoids in subtribe Centaureinae (Cass.) Dumort (tribe Cardueae, Asteraceae): Distribution, 13C NMR spectral data and biological properties

et al. 2013

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“…The structural importance of the γ-lactone moiety of DHCL for its biological activity was also suggested for the seed germination of parasitic plant Orobanche cumana [21]. Costunolide as well as DHCL have been reported to be part of a major functional group conferring various biological activities in the sesquiterpene lactones in both animals and plants [22][23][24][25][26][27]. Hence, it may be possible to explain why the exocyclic methylene double bond conjugated with a γ-lactone ring is essential for the biological activities of sesquiterpene lactones.…”

Section: Discussionmentioning

confidence: 99%

Isolation and identification of polar auxin transport inhibitors from Saussurea costus and Atractylodes japonica

et al. 2017

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An intensive survey of naturally-occurring regulators of polar auxin transport (PAT) was conducted in two oriental medicinal species from the Asteraceae, Saussurea costus and Atractylodes japonica, using the radish hypocotyl bioassay system and physicochemical analyses. Costunolide and santamarine were identified as well as dehydrocostus lactone from S. costus roots, and atractylenolide II and (+)-eudesma-4(14),7(11)-dien-8-one from Atractylodes japonica rhizomes as physiologically novel compounds possessing inhibitory activities of PAT. Costunolide and santamarine showed ca. 40% inhibition of PAT in the radish hypocotyl segments at a dose of 2.5 μg/plant and 1 μg/plant, respectively. Inhibitory effects of atractylenolide II and (+)-eudesma-4(14),7(11)-dien-8-one were ca. 10 times lower than those of costunolide and santamarine. Structure-activity relationships and possible mechanisms to inhibit PAT are also discussed.

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Costunolide and Dehydrocostus Lactone as Inhibitors of Killing Function of Cytotoxic T Lymphocytes

Cited by 85 publications

References 1 publication

Trypanocidal Terpenoids from Laurus nobilis L.

Trypanocidal Terpenoids from Laurus nobilis L.

Sesquiterpenoids in subtribe Centaureinae (Cass.) Dumort (tribe Cardueae, Asteraceae): Distribution, 13C NMR spectral data and biological properties

Isolation and identification of polar auxin transport inhibitors from Saussurea costus and Atractylodes japonica

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