1,721,031 research outputs found
A multiple criteria decision aiding system to support monitoring in a public administration
No full textCHEMICAL APPROACHES FOR IMPROVING DRUG DELIVERY OF KNOWN ANTICANCER COMPOUNDS
Full text linkDifferent classes of squalene conjugates have been prepared: the first one containing a disulfide bond that, in the presence of glutathione, is able to trigger the release of a drug unit, the second one containing a tripepidyl sequence selectively cleaved by plasmin and also able to release a drug unit, the last one containinf a fluorescein 5(6)isothiocyanate unit. These compounds are able to self-assemble in water and can improve the delivery of active drugs to tumor tissues and can be helpful in the understanding of nanoparticle cellular uptake
EVALUATING SOME AERODYNAMIC PARAMETERS OF THE FLIGHT TEST BED (FTB-X) IN HIGH ALTITUDE FLIGHT
No full textSome aerodynamic parameters of the FTB (Flight Test Bed) vehicle, designed at CIRA in
the frame of the program named PRORA, have been evaluated in the intervals of altitude
from 100 to 120 km and angle of attack from –10 to 40 deg., in symmetric flow and clean
configuration. Due to the failure of the Navier-Stokes equations to solve the flow field in
rarefied regimes, the computation relied on a Direct Simulation Monte Carlo (DSMC) code.
As the aim of the work is providing useful information for planning the mission tagged SRT
(Sub-orbital Reentry Test), the analysis focused on global aerodynamic coefficients (lift, drag
and moment) and local quantities (heat flux and stress) on the most exposed surfaces (i.e.
nose and leading edges of the wing and of the rudder). These parts will be made of Ultra
High Temperature Ceramic (UHTC) material, thus the combined effect of heat flux and
stress could be critical for their integrity and therefore for the safety of the vehicle. The
present results showed that: the maximum value of the lift to drag ratio, meet at an altitude
of 100 km and at an angle of attack of 30 deg. is 0.6, the maximum values of heat flux and
stress on the nose are 2656 W/m2 and 3.3 N/m2, on the leading edges of the wing are 1891
W/m2 and 2.4 N/m2, of the rudder are 1600 W/m2 and 2.1 N/m2. The lift to drag ratio is much
lower than the one predicted by means of Euler calculation (2.5), putting in evidence the
unacceptability of Euler calculation at these altitudes. Also the heat flux is considerably far
from the target value of 650 kW/m2, expected from continuum calculation, at an altitude of
about 25 km. Furthermore as the nose is the most loaded part of the vehicle, from a thermal
and a mechanical point of view, detailed profiles of the heat flux and of the stress are
provided along the windward surface in the range of angle of attack from 0 to 40 deg
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
Natural Products as Scaffolds for the Modulation of Topoisomerase I
No full textTwo natural products, Camptothecin (1, Figure 1), an alkaloid isolated from the Chinese tree Camptotheca acuminate Dence,1 and Evodiamine (2), an alkaloid isolated from the dried fruit of Evodia rutaecarpa (Juss.) Benth (E. rutaecarpa),2 are characterized by antitumoral activity, targeting the DNA topoisomerase I,3-5 an ubiquitous and essential enzyme for topological DNA modification during a number of critical cellular process in mammals.6
However, their therapeutic application is hindered because of poor aqueous solubility and high in vivo hepatoxicity. Subsequently, the structural modification of the natural Camptothecin and Evodiamine is crucial for the improvement of their pharmacological and pharmacokinetic profile.7-10
Figure 1. Structure of camptothecin and evodiamine and images taken from modeling studies.11
In our interest, for the synthesis of various derivatives of the natural compounds we focused on position 7 of the Camptothecin, and on position 5 of the Evodiamine moiety (Figure 2).
Experimental
In the case of Camptothecin, the reactivity of position 7 gave us the possibility to obtain 7-hydroxymethyl camptothecin that by reaction with hydrobromic acid resulted in the corresponding bromoderivative. We then turned our attention toward the formation of C-S bond that resulted as a not trivial issue. The solution of the problem gave us the possibility to obtain 3 different compounds stable enough to be submitted to different biological assays. Antiproliferative activity and topoisomerases inhibition were investigated and the results moved us to study the cellular response to the DNA damage and their influence on angiogenesis. With a similar approach a library of 11 compounds has been prepared by introduction of a carboxylic group at position 5 of evodiamine. The biological data have been compared with the suggestion deriving from modeling studies.
Figure 2.
Results and discussion
In the case of camptothecin derivatives, the results of cellular studies and the molecular modeling analysis indicated that the 7-modified camptothecin derivatives fully maintained the biological activity and the same feature of drug-target interaction of the natural compound. This conclusion is also supported by the biochemical characterization indicating a comparable ability to induce DNA damage. These observations support the view that the 7-position is favourable for safe introduction of suitable side chains without detrimental effects. In the case of evodiamine derivatives the preliminary results regarding the antoproliferative activity require further investigation that are ongoing.
References
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[2] Asahina, A., Kashiwaki, K., Yakugaku Zasshi, 405 (1915), 1293; Chem. Abstr., 10 (1916), 607.
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[4] Liu, L.F., Desai, S.D., Li, T.K., Mao, Y., Sun, M., Sim, S.P., Ann. N. Y. Acad. Sci., 922 (2000), 1-10.
[5] Dong, G., Sheng, C., Wang, S., Miao, Z., Yao, J., Zhang, W., J. Med. Chem., 53 (2010), 7521-2531.
[6] Pommier, Y., Nat. Rev. Cancer, 6 (2006), 789-802.
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[10] Chen, Z., Hu, G., Li, D., Chen, J., Li, Y., Zhou, H., Xie, Y., Bioorg. Med. Chem., 17 (2009), 2351–2359.
[11] The image of the docked position of evodiamine has been taken from Dong, G., Sheng, C.; Wang, S., Miao, Z., Yao, J., Zhang, W. J. Med. Chem 53 (2010), 7521-7531
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