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Synthesis and photobiological activity of new methylpsoralen derivatives.
No full textThe synthesis and the photobiological activity of two new derivatives of psoralen (3,4′-dimethylpsoralen and 3,4′,8-trimethylpsoralen) has been described. They are congeners of the monofunctional linear furocoumarin 3,4′-dimethyl-8-methoxypsoralen. Both compounds bind very efficiently to DNA, the extent of this process being modulated by the nature of substituents at position 8. The number of photolesions is linearly related to adenine—thymine content of the nucleic acid which indicates lack of specificity for particular sequences of the nucleic acid. The structural arrangement of DNA (single stranded, double stranded, nucleosomes and chromatin) plays an additional role in affecting the photobinding process. Unlike their 8-methoxy congener the new derivatives cross-link DNA to a substantial extent. Their photobiological properties, including erythema formation, reflect very closely those of 8-methoxypsoralen (8-MOP). The conclusion can be drawn that 3,4′-dimethyl-8-MOP represents a unique derivative in its family
Sequence specificity of psoralen photobinding to DNA: a quantitative approach
No full textThe effect of different DNA sequences on the photoreaction of various furocoumarin derivatives was investigated from a quantitative poin of view using a number of selfcomplementary oligonucleotides. The furocoumarins included classical bifunctional derivatives, such as 8-methoxy and 5-methoxypsoralen, as well as monofunctional compounds, such as angelicin and benzopsoralen. This approach, in combination with footprinting studies, appears to be quite useful for a quantitative investigation of the process of covalent binding of psoralens to specific sites in DNA
Synthesis and biological evaluation of some 5-substituted 11H- pyrido[3,2-a]carbazole derivatives.
No full textPhotobiological 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
Photoreaction of psoralen derivatives with structurally organized DNA
No full textThe DNA-photobinding process of a number of psoralen derivatives has been investigated using different nucleic acid structures, such as double helical DNA, nucleosomes, and chromatin under various ionic strength conditions
"Synthesis, DNA binding and in vitro antiproliferative activity of quinazobenzimidazole derivatives as potential antitumor agents".
No full text"Synthesis of new indolo[3,2-c][1,8]naphthyridine derivatives as antiproliferative agents"
No full textPharmacological characterization of a new Ca2+ sensitizer
Full text linkThe benzimidazole molecule was modified to synthesize a Ca(2+) sensitizer devoid of additional effects associated with Ca(2+) overload. Newly synthesized compounds, termed 1, 2, 3, 4, and 5, were evaluated in spontaneously beating and electrically driven atria from reserpine-treated guinea pigs. Compound 3 resulted as the most effective positive inotropic agent, and experiments were performed to study its mechanism of action. In spontaneously beating atria, the inotropic effect of 3 was concentration-dependent (3.0 microM-0.3 mM). Compound 3 was more potent and more active than the structurally related Ca(2+) sensitizers sulmazole and caffeine, but unlike them it did not increase the heart rate. In electrically driven atria, the inotropic activity of 3 was well preserved and it was not inhibited by propranolol, prazosin, ranitidine, pyrilamine, carbachol, adenosine deaminase, or ruthenium red. At high concentrations (0.1-1.0 mM) 3 inhibited phosphodiesterase-III, whereas it did not affect Na(+)/K(+)-ATPase, sarcolemmal Ca(2+)-ATPase, Na(+)/Ca(2+) exchange carrier, or sarcoplasmic reticulum Ca(2+) pump activities of guinea pig heart. In skinned fibers obtained from guinea pig papillary muscle and skeletal soleus muscle, compound 3 (0.1 mM, 1 mM) shifted the pCa/tension relation curve to the left, with no effect on maximal tension and no signs of toxicity. Compound 3 did not influence the basal or raised tone of guinea pig isolated aorta rings, whose cells do not contain the contractile protein troponin. The present results indicate that the inotropic effect of compound 3 seems to be primarily sustained by sensitization of the contractile proteins to Ca(2+)
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
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