In continuing our research with cytotoxic and pesticidal components from the stem bark of the North American paw paw, Asimina triloba, the novel cytotoxic monotetrahydrofuran Annonaceous acetogenins, ...cis- and trans-annonacin-A-one, cis- and trans-gigantetrocinone and cis-isoannonacin, in addition to the known compounds, trans-isoannonacin and squamolone, have been identified. Brine shrimp lethality testing was used to direct the fractionation. The structures were elucidated by spectral analysis and/or chemical synthesis. These acetogenins have potent cytotoxicities against the human tumour cell lines of A-549 (lung carcinoma), MCF-7 (breast carcinoma) and HT-29 (colon adenocarcinoma).
The Great Lakes Fishery Commission (GLFC) is considering greater use of low‐head barrier dams on stream tributaries of the Laurentian Great Lakes to control populations of sea lampreys Petromyzon ...marinus. The impact of these barriers on nontarget fishes is not known. A mark–recapture study on four Lake Ontario streams examined movements of fishes in streams with (barrier) and without (reference) low‐head barriers. A significantly lower proportion of fishes moved across a real barrier on barrier streams than across a hypothetical barrier on reference streams (0.15 versus 0.50, respectively). The impact of the barriers on movement was more pronounced in spring and fall than in summer. However, the likelihood of fishes moving versus not moving between sample segments on either side of a barrier location (but not across the barrier) did not differ significantly between barrier and reference streams. The upstream (longitudinal) decline in species richness was greater for barrier streams than for reference streams in each season. At both interspecific and intraspecific levels, mean total lengths of fish traversing real barriers were significantly greater than the mean total lengths of fish traversing hypothetical barriers. Our findings demonstrate that low‐head barriers restrict the movements of some fishes and suggest this restriction affects assemblage structure above the barrier.
The preparation of sterically hindered and polyfunctional C(alpha,alpha)-disubstituted alpha-amino acids (alpha alpha AAs) via alkylation of ethyl nitroacetate and transformation into derivatives ...ready for incorporation into peptides are described. Treatment of ethyl nitroacetate with N,N-diisopropylethylamine (DIEA) in the presence of a catalytic amount of tetraalkylammonium salt, followed by the addition of an activated alkyl halide or Michael acceptor, gives the doubly C-alkylated product in good to excellent yields. Selective nitro reduction with Zn in acetic acid or hydrogen over Raney Ni gives the corresponding amino ester that, upon saponification, can be protected with the fluorenylmethyloxycarbonyl (Fmoc) group. The first synthesis of an orthogonally protected, tetrafunctional C(alpha,alpha)-disubstituted analogue of aspartic acid, 2,2-bis(tert-butylcarboxymethyl)glycine (Bcmg), is described. Also, the sterically demanding C(alpha,alpha)-dibenzylglycine (Dbg) has been incorporated into a peptide using solid-phase synthesis. It was found that once sterically congested Dbg is at the peptide N-terminus, further chain extension becomes very difficult using uronium or phosphonium salts (PyAOP, PyAOP/HOAt, HATU). However, preformed amino acid symmetrical anhydride couples to N-terminal Dbg in almost quantitative yield in nonpolar solvent (dichloroethane-DMF, 9:1).
Gigantetronenin 1 and gigantrionenin 6, two new monotetrahydrofuran Annonaceous acetogenins each possessing a double bond along the hydrocarbon chain, have been isolated from the bark of ...Goniothalamus giganteus by the use of brine shrimp lethality for bioactivity-directed fractionation. The structures were elucidated based on spectroscopic and chemical methods. Compounds 1 and 6 both show selective and potent cytotoxicities to human tumor cells in culture as well as toxicity to brine shrimp. A known cytotoxic acetogenin, annomontacin 11, was also isolated from this plant. The biogenetic pathway of the acetogenins from G. giganteus is discussed.
Novel Radiochromic Films for Clinical Dosimetry McLaughlin, W.L.; Puhl, J.M.; Al-Sheikhly, M. ...
Radiation protection dosimetry,
07/1996, Letnik:
66, Številka:
1-4
Journal Article, Conference Proceeding
Recenzirano
New transparent radiochromic films, GafChromic MD-55 and NMD-55, which turn from colourless to deep blue upon irradiation, have been designed particularly for measuring radiation therapy absorbed ...doses (1 Gy to 100 Gy). They are also useful for high resolution mapping of dose distributions, radiographic imaging, treatment planning dosimetry, beam penumbra measurements, and interface dosimetry with ionising photons, electrons and protons. The gamma ray responses are linear with dose in terms of increase of optical absorbance at 670, 633 and 600 nm and are independent of absorbed dose rate and relative humidity. The radiochromic images show a slight gradual post-irradiation increase in absorbance especially during the first 24 h. In addition, there is a small but predictable variation of sensitivity with temperature, both during irradiation and during spectrophotometry. The films also have a slight sensitivity to ultraviolet radiation (250 to 350 nm) in direct sunlight. Experiments with X ray beams show no appreciable energy dependence relative to dose in water at photon energies greater than 100 keV, but they have a sensitivity that gives readings of about 60% of the dose in water for photons at 20 to 40 keV.
An oligonucleotide has been synthesized that contains a single bridging 5'-phosphorothioate at an RNA linkage (5'-ApCpGpGpTpCpTprCpsApCpGpApGpC-3'). This new phosphodiester linkage is found to be ...particularly susceptible to cleavage when compared with the corresponding oxo, deoxy and thiodeoxy derivatives. Divalent metal cations were observed to dramatically increase the cleavage rate. The products of the cleavage under a variety of conditions are a 5'-thiol-containing fragment (6mer) and a 2',3'-cyclic phosphate-containing fragment (8mer). The pseudo-first order rate constant, kobs, for cleavage at pH 7.5 (50 mM Tris-HCI) in the presence of 5 mM EDTA is 1.5 x 10(-4)/min. In the presence of 5 mM metal dichloride and 50 mM Tris-HCI, pH 7.5, the relative cleavage rate enhancements are 10, 24, 71, 98, 370 and 3400 for Mg2+, Ca2+, Mn2+, Co2+, Zn2+ and Cd2+ respectively. The rate enhancements correlate well with Pearson's HSAB principle, suggesting that cleavage is mediated in part by coordination of the metal to the 5'-mercapto leaving group. RNA linkages containing bridging 5'-phosphorothioates should prove valuable for studying the mechanistic details of a variety of RNA cleaving agents, such as ribozymes.
The exchangeable N1 imino protons of two pseudouridine (Ψ) bases located at adjacent Internal positions within an undecamer RNA duplex (5 AUA-CψψACCUG/3 UAUGAAUGGUC) can report on the environment of ...the major groove of an A-form double-stranded nucleic acid. The ψN1 Imlno protons of these residues (which are not involved in interstrand Watson-Crick hydrogen bonding) are protected from chemical exchange with the solvent water and thus are observable in the proton NMR spectrum in H2O (1). These protons will exchange readily at Increased pH values or upon thermal denaturation of the duplex. The longitudinal (T1) relaxation times of the ψN1 imino protons In 100 mM NaCI or in 10 mM MgCI2 and 100 mM NaCI are approximately two-fold faster than those of the ψN3 imino protons which are Involved in Watson-Crick base pairing. With the addition of spermkJine, the ψN1 imino protons become readily exchangeable at a temperature some 20°C below the melting temperature of the duplex.
Asimicin and a new cytotoxic Annonaceous acetogenin, venezenin 1, were isolated from the bark of Xylopia aromatica by bioactivity-directed fractionation using lethality to brine shrimp. Compound 1 ...represents an unusual type of C37 Annonaceous acetogenin, lacking either tetrahydrofuran (THF) or epoxide rings and possessing a double bond located two methylenes away from a vicinal diol in the hydrocarbon chain. The structure of 1 was elucidated by 1H- and 13C-nmr, COSY, single-relayed COSY, and by HMBC techniques, and derivatization. Annomontacin 10-one 6 and 18/21-cis-annomontacin-10-one 7, two semi-synthetic mono-THF acetogenins were prepared from 1. These acetogenins showed cytotoxicity, comparable or superior to adriamycin, against three human solid tumor cell lines. Reduction of the 10-keto of 1 to the racemic OH-10 derivative enhanced the bioactivity, as did the conversion of 1 to 6 and 7. Venezenin 1, like other Annonaceous acetogenins, showed inhibition of oxygen uptake by rat liver mitochondria and demonstrated that the THF ring may not be essential to this mode of action.
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