Studies on the antitumor-promoting activity of naturally occurring substances. II. Inhibition of tumor-promoter-enhanced phospholipid metabolism by umbelliferous materials

Ninety-five extracts prepared from 14 kinds of Umbelliferous materials were studied to determine their effects on tumor-promoter-induced phenomena in vitro. Of the materials, 5 Chinese crude drugs, two Bai-Hua Qian-Hu classified as Q-I and Q-II types, the root of Peucedanum praeruptorum Dunn., Zi-Hua Qian-Hu, the root of P. decursivum Maxim., Tang-Bai-Zhi, the root of Angelica dahurica Benth, et Hook. var. pai-chi Kimura, Hata et Yen., Dang-Gui, the root of A. acutiloba Kitagawa and 2 Umbelliferous plants, ashita-ba. A. keiskei Koidz., and ama-nyuu, A. edulis Miyabe, showed potent inhibitory effects on 12-O-tetradecanoylphorbol-13-acetate (TPA)-stimulated 32Pi incorporation into phospholipids of cultured cells. From the active fraction of the crude drug "Tang-Bai-Zhi," imperation (1), isoimperatoin (2), oxypeucedanin (3), pabulenol (4), neobyakangelicol (5) and byakangelicin (6) were identified as active or inactive principles. Compound 4 had not previously been isolated from Tang-Bai-Zhi, A. dahurica var. pai-chi. We also discuss the structure-activity relationship among the above 6 kinds of linear-type furanocoumarins, together with 3 kinds of antitumor-promoter coumarins having the same skeleton, psoralen (7), bergapten (8) and xanthotoxin (9), obtained from "ashita-ba" (eaten as a vegetable in Japan). Among the compounds in the present experiment, compounds 1 and 2 showed potent inhibitory activity at the concentration of 50 micrograms/ml and 3-9 were found to have less or no activity.     

Preparation of organic-inorganic composites containing rod-like phthalocyanine polymers

Sol-gel polymerization of tetraethoxysilane in the presence of amphiphilic phthalocyanine polymer 2 produced organic-inorganic composites with the rod-like phthalocaynine polymers incorporated within ordered hexagonal channels.     

Studies on inhibitors of skin tumor promotion. XI. Inhibitory effects of flavonoids from Scutellaria baicalensis on Epstein-Barr virus activation and their anti-tumor-promoting activities.

To search for possible anti-tumor-promoters, fourteen flavones obtained from the root of Scutellaria baicalensis were examined for their inhibitory effects on the Epstein-Barr virus early antigen (EBV-EA) activation by a short-term in vitro assay. Among these flavones, 5,7,2'-trihydroxy- and 5,7,2',3'-tetrahydroxyflavone showed remarkable inhibitory effects on the EBV-EA activation, and the effect of the latter on Raji cell cycle was also examined by flow cytometer. These two flavones exhibited remarkable inhibitory effects on mouse skin tumor promotion in an in vivo two-stage carcinogenesis test.     

Efficient solid-phase synthesis of clavulones via sequential coupling of alpha- and omega-chains

We describe an efficient solid-phase synthesis of clavulones via the sequential coupling of the alpha- and omega-chains, involving two separate carbon-carbon bond-forming steps. The tetrahydropyranyl linker survived these reaction conditions and was cleaved without decomposing the unstable cross-conjugated dienones. Our methodology has allowed us to prepare six clavulone derivatives that are varied within the alpha-chain.     

Mechanism of ionization and initial fragmentation in electron impact mass spectra of 3-halogenobenzanthrones

Electron-impact mass spectra of 3-halogenobenzanthrones (halogen X = Cl, Br, I) were measured and ionization efficiency curves and three kinds of linked-scan spectra were obtained for several fragment ions. The fundamental mechanisms of ionization and initial fragmentation were interpreted by the penetration length of an impacting electron or the density distribution on the molecular surface of a rejected electron and its orbital energy. The apparent ionization energy (IE) of a singly charged molecular ion seems to be the lower one of non-bonding electrons on O or X, and that of a doubly charged molecular ion the sum of three terms, the IE of non-bonding electron on O, that on X and the electrostatic repulsion between two positive charges. Two competing pathways of decomposition from the molecular ion M^+· to an ion [M - CO,- X]⁺ were observed: one is the initial detachment of CO in chloro and bromo compounds and the other is the initial elimination of the iodine atom in the iodo compound. The sequence of these reactions was confirmed by metastable ion analysis with linked-scan spectra and the relative magnitudes of the appearance energies. They can be explained by the driving force of a localized positive charge or unpaired electron on a heteroatom.     

The C-glucosyl bond of puerarin was cleaved hydrolytically by a human intestinal bacterium strain PUE to yield its aglycone daidzein and an intact glucose

C-Glycosides are usually resistant against acidic hydrolysis and enzymatic treatments because C-1 of the sugar moiety is directly attached to the aglycone by C-C bonding. Nevertheless, a human intestinal bacterium, strain PUE, can cleave the C-glucosyl bond of puerarin to yield its aglycone daidzein. To clarify the mechanism of the cleaving reaction, we tried to identify the structure of the metabolite derived from the sugar moiety of puerarin. To detect it easily, deuterium labeled puerarin, [6″,6″-D(2)]puerarin, was prepared in 7 steps. Sugars contained in a metabolite mixture from [6″,6″-D(2)]puerarin was analyzed by an HPLC-electrospray ionization (ESI)-MS method after treatment of sugars with 1-phenyl-3-methyl-5-pyrazolone (PMP). Since deuterium labeled glucose was detected in the metabolite mixture of [6″,6″-D(2)]puerarin, we concluded that puerarin was metabolized to daidzein and an intact glucose by strain PUE. As C-1 of the sugar was hydroxylated instead of hydrogenating, C-glucosyl bond-cleaving reaction is not reduction but hydrolysis. This is the first report of revealing the reaction manner and the exact products of C-glucosyl bond-cleaving reaction.     

Structures of euglobal-G1, -G2, and -G3 from Eucalyptus grandis, three new inhibitors of Epstein-Barr virus activation

Three new euglobals with acylphloroglucinol-monoterpene structures, named euglobal -G1 (1), -G2 (2), and -G3 (3) were isolated from the chloroform extract of the juvenile leaves of Eucalyptus grandis (Myrtaceae). The structures of these new compounds were determined on the basis of their spectral data. The compounds strongly inhibited the Epstein-Barr virus activation.     

PHOTOCYTOTOXICITY OF WATER-SOLUBLE METALLOPORPHYRIN DERIVATIVES

Abstract— A new water-soluble porphyrin derivative, 2,4-bis(1-decyloxyethyl)-deuteroporphyrinyl–6,7-bisaspartic acid(C–10-DP), and its metal complexes (Ga, In, Sn, Zn, Mn, Cu, Ni and Fe) were examined for their physicochemical properties (absorption, fluorescene, triplet lifetime and partition coefficient) and photocytotoxicity on HeLa cells. The five derivatives with longer(>1ms) triplet lifetimes (free base, Zn, Ga, In and Sn complexes) exhibited remarkable photocytotoxicity, and the other derivatives (Mn, Cu, Ni and Fe), which had or were deduced to have fairly short (<0.01 ms) triplet lifetimes, manifested no photocytotoxicity, indicating that the triplet lifetime of these derivatives played a significant role in their photocytotoxicity. Cellular fluorescence due to C10-DP and its gallium complex was observed mainly on the plasma membrane at the concentrations showing significant photocytotoxicity with low (<32.6%) cytotoxicity in the dark(2–10 μM).     

Heteroleptic [Bis(oxazoline)](dipyrrinato)zinc(II) Complexes: Bright and Circularly Polarized Luminescence from an Originally Achiral Dipyrrinato Ligand

Heteroleptic zinc(II) complexes synthesized using achiral dipyrrinato and chiral bis(oxazoline) ligands show bright fluorescence with quantum efficiencies of up to 0.70. The fluorescence originates from the ¹π–π^* photoexcited state localized exclusively on the dipyrrinato ligand. Furthermore, the luminescence is circularly polarized despite the achirality of the dipyrrinato ligand. Single‐crystal X‐ray structure analysis discloses that the chiral bis(oxazoline) ligand undergoes intramolecular π–π stacking with the dipyrrinato ligand, inducing axial chirality in the dipyrrinato moiety.