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. The taxonomic status of M. paniculata var. zollingeri is briefly discussed, along with its similarity to M. paniculata.

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. Furthermore, the percentage of apoptotic cells was decreased with increasing rates of nobiletin to paclitaxel and carboplatin. These findings were considered to be attributed to the ability of nobiletin to regulate cells in the G1 phase, which escaped cell death initiated by paclitaxel and carboplatin. An antitumor activity assay showed that this combination significantly suppressed the growth of subcutaneous A549 tumor xenografts in nude mice.

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

Synthesis of dehydoriso-ß-lapachone (1) in both racemic and enantioenriched forms is achieved starting from reduced naphthoquinone equivalents. As for the synthesis of enantioenriched dehydroiso-ß-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-(ß)-naphthoquinone was carried out by acidic ring-opening reaction of the epoxynaphthalene and the following diammonium cerium(IV) nitrate (CAN) oxidation. The absolute configuration of naturally occurring (-)-dehydroiso-ß-lapachone was finally determined as (R) by comparing the measured optical rotation value of the synthetic (R)-dehydroiso-ß-lapachone.

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. The following new compounds of constituents were found: dimeric coumarins, dimeric acridone alkaloids, and acridone-coumarin dimers. Auraptene and nobiletin are known as useful constituents of the peel of Citrus plants for cancer chemoprevention. However, we found that 3,5,6,7,8,3',4'-heptamethoxyflavone (HPT) has both antitumor promotion and initiation activities and is more effective than auraptene and nobiletin. We synthesized pentaallyl quercetin (QPA), a useful antitumor compound that has the additional effects of a P-glycoprotein (P-gp) inhibitor. The inhibitory effects of QPA on P-gp were more effective than those of the typical P-gp inhibitors cyclosporin A and verapamil. Both HPT and QPA have antitumor promotion activity and are potential candidates for effective multidrug resistance agents in cancer chemotherapy.

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)

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. Furthermore, lupinifolin (5) exhibited a marked inhibitory effect on mouse skin tumor promotion in an in vivo two-stage carcinogenesis test. These results indicate that some of these prenylated flavanones might be valuable as potential cancer chemopreventive agents (anti-tumor promoters).