1,720,987 research outputs found
Photobiological activity of 3,4'-dimethyl-8-methoxypsoralen, a linear furocoumarin with unusual DNA-binding properties
No full textThe furocoumarin derivative 3,4'-dimethyl-8-methoxypsoralen (DMe-8-MOP) exhibits remarkable antiproliferative activity, but is devoid of skin phototoxicity. To gain insight into this peculiar behaviour we investigated non-covalent and covalent binding of DMe-8-MOP to calf thymus DNA, along with DNA-synthesis inhibition and mutagenic activity. The non-covalent interaction of DMe-8-MOP with the nucleic acid is quite poor as shown by equilibrium dialysis, spectroscopic, chiroptical and hydrodynamic techniques. However, it exhibits relevant photobinding ability to DNA using both isolated nucleic acid samples and cellular systems. Unlike the large majority of congeners, DMe-8-MOP undergoes predominantly photochemical monoaddition to the double helical polynucleotide. Upon examination of the products obtained by enzymatic hydrolysis of DMe-8-MOP photomodified DNA, the formation of an unusual furan side adduct is proposed, which could account for the peculiar photochemical and photobiological properties of the 3,4'-dimethyl furocoumarin derivative
Antitumor activity and nephrotoxicity of a new platinum(II) complex with pyridine and dithiocarbamate
No full text
4,6,4'-Trimethylangelicin induces inter-strand cross-links in mammalian cell DNA
No full text4,6,4'-Trimethylangelicin, a well-known effective photosensitizer described as a pure monofunctional reactant with DNA, can induce interstrand cross-links in mammalian cell DNA in vivo (about 15% relative to 8-methoxypsoralen), as observed using alkaline elution and Chinese hamster ovary cells. Experiments performed using the two-step irradiation method and HeLa cells support these data. In contrast with 4,6,4'-trimethylangelicin, 4'-methylangelicin and 4,4'-dimethylangelicin do not form interstrand cross-links. These results are consistent with those recently reported by Chen et al. (X. Chen, J. Kagan, F. Dall'Acqua, D. Averbeck and E. Bisagni, J. Photochem. Photobiol. B: Biol, 22 (1994) 51-57) using pBR322 and M13 DNA. The cross-linking ability of 4,6,4'-trimethylangelicin does not seem to be related to a particular feature of these DNAs but to the compound itself
Synthesis and Biological Activity of Hydroxymethyl and Diethylaminomethylbenzopsoralens.
No full textSome benzopsoralens, carrying a hydroxymethyl or a diethylaminomethyl group at the 3, 5, 8, and 11 positions, were prepared, and their biological activity was compared with that of 4-(hydroxymethyl)benzopsoralen (BP). 5-(Hydroxymethyl)benzopsoralen (7b), 11-(hydroxymethyl)benzopsoralen (7c), and 11-(diethylaminomethyl)benzopsoralen (8c) induced marked antiproliferative effects in mammalian cells by simple incubation in the dark; this activity appeared to be related to their ability to inhibit topoisomerase II. Benzopsoralens appeared to be more active, especially BP and 7c, upon WA activation. Compounds carrying a methyl group at the 4 position together with a hydroxymethyl Or diethylaminomethyl at the 8 position (7d and 8d, respectively) were also effective, although to a lower extent; instead, a substituent at the 3 position canceled all activity. Benzopsoralens did not induce interstrand cross-links in DNA in vitro, as seen in the induction of cytoplasmic > mutations and double-strand breaks in yeast. This behavior is also compatible with their low mutagenic activity in E. coli WP2 and with the absence of any phototoxicity on the skin. For these features, benzopsoralens seem to be interesting potential drugs for PUVA photochemotherapy and photopheresis. The activity shown in the dark is not sufficient for their possible use as antitumor drugs, but it does offer a new model for the study of topoisomerase inhibitors
Preparation and properties of monomethoxy poly(ethylene glycol)-doxorubicin conjugates linked by an amino acid or peptide as spacer
No full textPolymeric doxorubicin prodrugs were prepared linking monomethoxy
poly(ethylene glycol), 5000 D molecular weight, to the doxorubicin amino group,
using an amino acid or a peptide as a spacer arm. As spacers glycine, Lphenylalanine,
L-tryptophan and glycil-L-valil-L-phenylalanine were used. The
conjugates showed enhanced stability to alkaline degradation compared to the free
doxorubicin. Towards Ehrlich solid tumor in mice the glycin spaced derivative was
devoid of activity, whereas the phenylalanine and tryptophan derivatives were 20%
and 16% active and the tripeptide one 50% active with respect to free doxorubicin.
On the other hand the derivatization was accompanied by a great decrease of
toxicity in mice with respect to the free drug. Doxorubicin was not released from
conjugates by chymotrypsin incubation or in plasm
Synthesis and biological properties of some 2H-1-benzopyran [7,8-b][1,4]benzodioxin-2-ones.
No full textThe synthesis of 2H-benzopyrano[7,8-b][1,4]tetrahydrobenzodioxin-2-ones and 2H-benzopyrano[7,8-b][1,4]benzodioxin-2-ones is reported. This class of compounds, prepared with the aim of obtaining new monofunctional photosensitizing drug, appears to be ineffective upon UVA irradiation but shows a moderate but significant activity in the dark
Platinum(II) and palladium(II) complexes with dithiocarbamates and amines: synthesis, characterisation and cell assay
No full textThe [M(ESDT)Cl](n) (M=Pd or Pt; ESDT=EtO2CCH2(CH3)NCS2-, methylamino-acetic acid ethyl ester-dithiocarboxylate) species have been reacted with various amines (py, pyridine: PrNH2, n-propylamine; c-BuNH2, cyclobutylamine; en, ethylenediamine) in dichloromethane or chloroform with the aim to obtain mixed ligand complexes. The neutral complexes [M(ESDT)(L)CI] (L=py, PrNH2 or c-BuNH2) and the ionic species ([M(ESDT)(L)(2)]Cl and [M(ESDT)(En)]Cl) have been isolated, and characterized by IR and proton NMR spectroscopies. The crystal structure of [Pd(ESDT)(PrNH2)Cl] has been determined by X-ray crystallography. The behaviour of the complexes in various solvents was described on the basis of the proton NMR spectra. The complexes and the dithiocarbamato intermediates have been tested for in vitro cytostatic activity against human leukemic HL-60 and HeLa cell
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Variations on the Author
Full text link“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
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