Age-dependent doses to members of the public from intake of radionuclides Part 4: Inhalation dose coefficients

Recent advances in annonaceous acetogenins

A urinary profile study of dietary phytoestrogens. The identification and mode of metabolism of new isoflavonoids.

Extracts of paw paw (Asimina triloba, Annonaceae) are among the most potent of the 3500 species of higher plants screened for bioactive compounds in our laboratories at Purdue University. The paw paw is a small tree native to eastern North America; its edible fruits (sometimes referred to as “Indiana Bananas”) have nurtured mankind for centuries. Activity-directed fractionation of the paw paw extracts, using the brine shrimp lethality bioassay, led to the isolation and molecular characterization of over 50 unique annonaceous acetogenins. Fractionation of extracts from related species resulted in the identification of over 150 additional acetogenins. The annonaceous acetogenins are derivatives of long-chain (C32 or C34) fatty acids. They are potent inhibitors of mitochondrial (complex I) as well as cytoplasmic (anaerobic) production of adenosine triphosphate (ATP) and the related nucleotides. The powerful cytotoxicity, in vivo antitumor, pesticidal, antimalarial, anthelmintic, piscicidal, antiviral, and an...

Paw Paw and Cancer: Annonaceous Acetogenins from Discovery to Commercial Products⊥

Infections with protozoan parasites are a major cause of disease and mortality in many tropical countries of the world. Diseases caused by species of the genera Trypanosoma (Human African Trypanosomiasis and Chagas Disease) and Leishmania (various forms of Leishmaniasis) are among the seventeen "Neglected Tropical Diseases" (NTDs) defined by the WHO. Furthermore, malaria (caused by various Plasmodium species) can be considered a neglected disease in certain countries and with regard to availability and affordability of the antimalarials. Living organisms, especially plants, provide an innumerable number of molecules with potential for the treatment of many serious diseases. The current review attempts to give an overview on the potential of such plant-derived natural products as antiprotozoal leads and/or drugs in the fight against NTDs. In part I, a general description of the diseases, the current state of therapy and need for new therapeuticals, assay methods and strategies applied in the search for new plant derived natural products against these diseases and an overview on natural products of terpenoid origin with antiprotozoal potential were given. The present part II compiles the current knowledge on natural products with antiprotozoal activity that are derived from the shikimate pathway (lignans, coumarins, caffeic acid derivatives), quinones of various structural classes, compounds formed via the polyketide pathways (flavonoids and related compounds, chromenes and related benzopyrans and benzofurans, xanthones, acetogenins from Annonaceae and polyacetylenes) as well as the diverse classes of alkaloids. In total, both parts compile the literature on almost 900 different plant-derived natural products and their activity data, taken from over 800 references. These data, as the result of enormous efforts of numerous research groups world-wide, illustrate that plant secondary metabolites represent an immensely rich source of chemical diversity with an extremely high potential to yield a wealth of lead structures towards new therapies for NTDs. Only a small percentage, however, of the roughly 200,000 plant species on earth have been studied chemically and only a small percentage of these plants or their constituents has been investigated for antiprotozoal activity. The repository of plant-derived natural products hence deserves to be investigated even more intensely than it has been up to present.

The Potential of Secondary Metabolites from Plants as Drugs or Leads Against Protozoan Neglected Diseases – Part I

For over three decades, mass spectrometry has played a central role for the structure elucidation of natural products because it can be used to determine the molecular weights and elemental compositions of substances with a wide range of chemical and physical properties In addition, if the molecular ion is formed with sufficient excitation energy, it will undergo a series of unimolecular reactions to give fragment ions, the relative abundances of which are normally unique to the structure of the molecular ion By understanding the general rules governing the fragmentation reactions, the types of functional groups present, as well as the manner in which they are joined to form a unique molecular structure may be deduced from the mass spectrum

Structure Elucidation of Natural Products by Mass Spectrometry

The structural elucidations of gigantetrocin and gigantriocin, two novel bioactive monotetrahydrofuran acetogenins with vicinyl hydroxyls are presented. These compounds are significantly and selectively cytotoxic to human tumor cells in culture and toxic to brine shrimp, and they inhibit the formation of crown gall tumors on potato discs, showing good potential for in vivo antitumor activities

Gigantetrocin and gigantriocin : two novel bioactive annonaceous acetogenins from goniothalamus giganteus

Absorption of calcium and magnesium endogenous to human milk, as well as calcium and magnesium added as an exogenous supplement to human milk, was determined in 9 very low birth wt infants. Human milk, intrinsically labeled with stable isotopic tracers of calcium and magnesium, was prepared by administering isotopic tracers intravenously to a lactating woman. Different isotopic tracers, which were representative of calcium and magnesium in the supplement (Enfamil Human Milk Fortifier, Mead Johnson Nutritional Div.), were added to the intrinsically labeled milk. The fortified milk, which was labeled with two calcium tracers and two magnesium tracers, was given orally to the test subjects in a single feeding. True absorption of calcium and magnesium was determined from differences between the doses of tracer ingested and the quantities of tracer excreted in the feces. Stable isotopic tracers were quantified by fast atom bombardment mass spectrometry. These results demonstrate that the fractional absorptions of calcium in the human milk and the added mineral supplement are 80 and 82%, respectively. A total of 89% magnesium endogenous to human milk and 86% of magnesium derived from the mineral supplement was absorbed by the VLBW infants.

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Absorption of calcium and magnesium from fortified human milk by very low birth weight infants

Gigantecin (I), a novel tetrahydroxy-di-tetrahydrofuran fatty acid γ-lactone (acetogenin), was isolated from an ethanolic extract of the stem bark ofGoniothalamus giganteus Hook. f., Thomas (Annonaceae), by means of activity-directed fractionation (brine shrimp lethality test). This new compound is extremely cytotoxic to human tumor cells, inhibits crown gall tumors on potato discs, and is active in an assay designed to detect antimitotic agents (9 ASK).

Gigantecin: a novel antimitotic and cytotoxic acetogenin, with nonadjacent tetrahydrofuran rings, from Goniothalamus giganteus (Annonaceae).

Sylvaticin (I), a new tetrahydroxy annonaceous acetogenin with nonadjacent tetrahydrofuran rings, has been isolated from the dried fruits ofRollinia sylvatica St. Hil. (Annonaceae). This compound is extremely cytotoxic to human tumor cells and shows promising insect control properties.

Ya-Mei Liu

Papers

Structure Elucidation of Natural Products by Mass Spectrometry

Gigantetrocin and gigantriocin : two novel bioactive annonaceous acetogenins from goniothalamus giganteus

Absorption of calcium and magnesium from fortified human milk by very low birth weight infants

Gigantecin: a novel antimitotic and cytotoxic acetogenin, with nonadjacent tetrahydrofuran rings, from Goniothalamus giganteus (Annonaceae).

Sylvaticin: a new cytotoxic and insecticidal acetogenin from Rollinia sylvatica (Annonaceae).