Coumarins from Murraya exotica collected in Egypt.

Four new coumarins, isomurralonginol senecioate (1), isomurralonginoic acid (2), murrangatin 2'-formate (3), and meranzin hydrate 2'-palmitate (4), were isolated from the vegetative branches of Murraya exotica together with 33 known compounds. The structures of the new compounds were determined from chemical and spectroscopic data.

Coumarins from Murraya paniculata var. zollingeri endemic to the Timor Islands.

Four new coumarins, murrangatin-1'-senecioate (1), 5-methoxypanial (2), mexoticin-2'-senecioate (3) and murralongic acid (4), were isolated from the leaves of Murraya paniculata var. zollingeri, together with 23 known coumarins. The structures of the new compounds were elucidated based on spectroscopic data.

Synergistic antitumor effect of a combination of paclitaxel and carboplatin with nobiletin from Citrus depressa on non-small-cell lung cancer cell lines.

Non-small-cell lung carcinomas do not sufficiently respond to cancer chemotherapeutic drugs. Combination effects of cancer chemotherapy drugs (paclitaxel and carboplatin) with nobiletin or powdered Shiikuwasha extract from Citrus depressa were examined by isobologram and combination index analyses. It was demonstrated that the combination generated a synergistic inhibitory effect against the proliferation of the human non-small-cell lung carcinoma cell lines A549 and H460 and that of the two chemotherapy drugs, paclitaxel was responsible for this synergistic effect.

Synthesis of biologically active (-)-dehydroiso-β-lapachone and the determination of its absolute configuration.

Synthesis of dehydoriso-β-lapachone (1) in both racemic and enantioenriched forms is achieved starting from reduced naphthoquinone equivalents. As for the synthesis of enantioenriched dehydroiso-β-lapachone, introduction of the asymmetric center was carried out by catalytic asymmetric epoxidation of the unfunctionalized trisubstituted olefin using Shi epoxidation diketal catalyst. The construction of isopropenylfurano-1,2-(β)-naphthoquinone was carried out by acidic ring-opening reaction of the epoxynaphthalene and the following diammonium cerium(IV) nitrate (CAN) oxidation.

Two new dimeric coumarins isolated from Murraya exotica.

Bismurrangatin and murramarin A, two new coumarins, were isolated from the vegetative branches of Murraya exotica. Murramarin A is a rare type of bicoumarin that connects two coumarin moieties by orthoester structure. The structures were elucidated based on spectroscopic methods, especially by 2D-NMR experiments.

[Chemical study of citrus plants in the search for cancer chemopreventive agents].

The constituents of Citrus plants were investigated to develop useful agents that are effective in cancer chemoprevention. We examined the roots and bark of the roots of various Citrus plants, resulting in the isolation of many novel compounds. Their structures were determined using spectroscopic methods, especially 2D-NMR spectra.

Antitumor-promoting activity of coumarins from citrus plants.

In order to identify antitumor-promoting agents, we performed primary in vitro screening of 31 coumarins isolated from 11 plants of the Citrus species (Rutaceae), examining their possible inhibitory effects on Epstein-Barr virus early antigen (EBV-EA) activation induced by 12- O-tetradecanoylphorbol-13-acetate (TPA) in Raji cells. Some of the 8-substituted coumarins, 8-formyl-7-hydroxycoumarin (5), osthenol (7), demethylauraptenol (8), osthenon (9) and dihydroosthenon (10), were found to significantly inhibit EBV-EA activation (IC50: 129-207 mol ratio/32 pmol TPA). Osthenol (7) exhibited a marked inhibitory effect on mouse skin tumor promotion in an in vivo two-stage carcinogenesis test.

Insect antifeedants from tropical plants: structures of dumnin and dumsenin.

Two novel A-seco limonoids, dumnin and dumsenin, were isolated from the methanolic extract of Croton jatrophoides by bioassay-guided fractionation, and the structures were determined by nuclear magnetic resonance, circular dichroism, and mass spectrometry experiments. These compounds showed potent antifeedant activity (PC(50) View Article and Find Full Text PDF

Two new dimeric acridone alkaloids from Glycosmis citrifolia.

Two new acridone dimers, glycobismines-F (1) and -G (2), were isolated from the roots of Glycosmis citrifolia collected in Taiwan. The structures of the new compounds were determined based on spectral analysis.

Cancer chemopreventive activity of flavanones on Epstein-Barr virus activation and two-stage mouse skin carcinogenesis.

To search for possible cancer chemopreventive agents from natural sources, we performed primary screening of ten flavanones isolated from plants belonging to Rutaceae and Leguminosae by examining their possible inhibitory effects on Epstein-Barr virus (EBV) early antigen activation induced by 12-O-tetradecanoylphorbol-13-acetate in Raji cells. All of the flavanones tested in this study showed inhibitory activity against EBV, without showing any cytotoxicity. Amorilin (3), which has three prenyl (3-methyl-2-butenyl) side-chains in the molecule, showed the most potent activity.

Isolation and identification of two new flavanones and a chalcone from Citrus kinokuni.

Two new flavanones and one chalcone were isolated from the peel of Citrus kinokuni Hort. ex Tanaka and identified as (2S)-5,6,7,8,4'-pentamethoxyflavanone (1), (2S)-5,6,7,3',4'-pentamethoxyflavanone (2) and 2'-hydroxy-3,4,3',4',6'-pentamethoxychalcone (3). The structures of new compounds were elucidated by spectroscopic analysis.

Inhibitory effect of flavonoid derivatives on Epstein-Barr virus activation and two-stage carcinogenesis of skin tumors.

To search for possible anti-tumor promoters, ten flavonoid derivatives (1-10) synthesized from morin and quercetin were examined for their inhibitory effects on the Epstein-Barr virus early antigen (EBV-EA) activation by a short-term in vitro assay. Of these compounds, pentaallyl ethers (9, 10) showed significant inhibitory effects on EBV-EA activation induced by the tumor promoter, 12-O-tetradecanoylphorbol 13-acetate. Further, quercetin pentaallyl ether (10) exhibited remarkable inhibitory effects on mouse skin tumor promotion in an in vivo two-stage carcinogenesis test.

In vitro absorption and metabolism of nobiletin, a chemopreventive polymethoxyflavonoid in citrus fruits.

The polymethoxyflavonoid (PMF), nobiletin (NOB), specifically occurs in citrus fruits, and is currently believed to be a promising anti-inflammatory and antitumor promoting agent. In the present study, we investigated the in vitro absorption and metabolism of NOB and compared them with those of the polyhydroxyflavonoid (PHF), luteolin (LT). NOB preferentially accumulated in a differentiated Caco-2 cell monolayer, which is a model for small intestinal epithelial cells, while LT did not.

Cancer chemopreventive activity of 3,5,6,7,8,3',4'-heptamethoxyflavone from the peel of citrus plants.

Nobiletin and 3,5,6,7,8,3',4'-heptamethoxyflavone (HPT), isolated from the peel of Citrus plants, were examined for the anti-tumor-initiating activity on two-stage carcinogenesis of mouse skin tumors induced by a nitric oxide donor, (+/-)-(E)-methyl-2-[(E)-hydroxyimino]-5-nitro-6-methoxy-3-hexenamide, as an initiator and 12-O-tetradecanoylphorbol-13-acetate as a promoter. HPT exhibited the remarkable anti-tumor-initiating effect on mouse skin and it suggested the possibility of HPT being a chemopreventive agent against nitric oxide (NO) carcinogenesis.

Inhibitory effect of flavonoids from citrus plants on Epstein-Barr virus activation and two-stage carcinogenesis of skin tumors.

To search for possible anti-tumor promoters, thirteen flavones (1-13) obtained from the peel of Citrus plants were examined for their inhibitory effects on the Epstein-Barr virus early antigen (EBV-EA) activation by a short-term in vitro assay. Of these flavones, 3,5,6,7,8,3',4'-heptamethoxyflavone (HPT) (13) exhibited significant inhibitory effects on the EBV-EA activation induced by the tumor promoter, 12-O-tetradecanoylphorbol 13-acetate (TPA). Further, compound 13 exhibited remarkable inhibitory effects on mouse skin tumor promotion in an in vivo two-stage carcinogenesis test.

Four new furanone-coumarins from Clausena excavata.

Four new furanone-coumarins, clauslactones-N (4), -O (5), -P (6) and -Q (7) were isolated from the leaves and twigs of Clausena excavata BURM. f. (Rutaceae) collected in Indonesia and their structures were elucidated by spectroscopic analysis.

Inhibitory effect of Epstein-Barr virus activation by Citrus fruits, a cancer chemopreventor.

To search useful compounds in Citrus fruit for cancer chemoprevention, we carried out a primary screening of extracts of fruit peels and seeds from 78 species of the genus Citrus and those from two Fortunella and one Poncirus species, which were closely related to the genus Citrus. These Citrus extracts inhibited the Epstein-Barr virus early antigen (EBV-EA) activation induced by 12-O-tetradecanoylphorbol 13-acetate (TPA) as a useful screening method for anti-tumor promoters. Our results indicated that Citrus containing substances may be inhibit susceptibility factors involved in the events leading to the development of cancer.

The antiproliferative effect of acridone alkaloids on several cancer cell lines.

Fifteen acridone alkaloids were examined for their antiproliferative activity toward monolayers and suspension of several types of cancer and normal human cell lines. As a result, atalaphyllidine (9), 5-hydroxy-N-methylseverifoline (11), atalaphyllinine (12), and des-N-methylnoracronycine (13) showed potent antiproliferative activity against tumor cell lines, whereas they have weak cytotoxicity on normal human cell lines. The structure-activity relationship established from the results revealed that a secondary amine, hydroxyl groups at C-1 and C-5, and a prenyl group at C-2 played an important role for antiproliferative activities of the tetracyclic acridones.

Acridones as inducers of HL-60 cell differentiation.

Fifteen acridone alkaloids were examined for their activity of induction of human promyelocytic leukemia cell (HL-60) differentiation. HL-60 cells were differentiated into mature monocyte/macrophage by atalaphyllidine (9), atalaphyllinine (12), and des-N-methylnoracronycine (13). The activities of NBT reduction, nonspecific esterase, and phagocytosis, were induced by 2.

Studies on the inhibitory effects of some acridone alkaloids on Epstein-Barr virus activation.

Twenty-five acridone alkaloids from Citrus plants were examined for their inhibitory effects on Epstein-Barr virus activation by a short-term in vitro assay. 5-Hydroxynoracronycine (20) and acrimarine-F (25) showed remarkable inhibitory effects.

Unique action of a modified weakly acidic uncoupler without an acidic group, methylated SF 6847, as an inhibitor of oxidative phosphorylation with no uncoupling activity: possible identity of uncoupler binding protein.

The potent weakly acidic uncoupler SF 6847 was modified by methylation of its phenolic OH group, and the effect of the resulting derivative, with no acid-dissociable group, on oxidative phosphorylation in rat liver mitochondria was examined. The methylated SF 6847 did not induce uncoupling at up to 40 microM, while SF 6847 uncoupled oxidative phosphorylation completely at about 20 nM, indicating that the acid-dissociable group is essential for uncoupling. The O-methylated SF 6847 at 20 microM did, however, inhibit state 3 respiration of mitochondria, although it did not inhibit electron-flow through the respiratory chain, ATPase activated by weakly acidic uncouplers or Pi-ATP exchange.

Antitumor agents, 79. Cytotoxic antileukemic alkaloids from Brucea antidysenterica.

Two cytotoxic antileukemic alkaloids, the new 1,11-dimethoxycanthin-6-one (3) and the known 11-hydroxycanthin-6-one (1), as well as the known canthin-6-one (2) were isolated from the stem of Brucea antidysenterica. The structures of 1-3 were determined from their spectral data and X-ray analysis of the o-bromobenzoate of 1.

Molecular basis of the protonophoric and uncoupling activities of the potent uncoupler SF-6847 [3,5-di-tert-butyl-4-hydroxybenzylidene)malononitrile) and derivatives. Regulation of their electronic structures by restricted intramolecular rotation.

We reported recently (Yoshikawa, K. and Terada, H. (1982) J.