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Solvent-Free Synthesis, DNA-Topoisomerase II Activity and Molecular Docking Study of New Asymmetrically N,N'-Substituted Ureas
Departamento de Química, Instituto de Ciências Exatas, Universidade Federal Rural do Rio de Janeiro, 23890-000, Seropédica, Rio de Janeiro, Brazil
* Author to whom correspondence should be addressed.
Received: 28 August 2012; in revised form: 26 September 2012 / Accepted: 26 October 2012 / Published: 1 November 2012
Abstract: A new series of asymmetrically N,N'-substituted ureas 20–25 was prepared using solvent free conditions, which is an eco-friendly methodology, starting with Schiff bases derived from cinnamaldehyde and p-substituted anilines, which are subsequently submitted to reduction reactions that afford the corresponding asymmetric secondary amines. All of the intermediates were prepared using solvent free reactions, which were compared to traditional methodologies. All of the reactions required a remarkably short amount of time and provided good yields when solvent free conditions were employed compared to other methodologies. The DNA-topoisomerase II-α (topo II-α) activity was evaluated in relaxation assays, which showed that all of the compounds inhibited the enzyme activity at 10 μM, except for urea 24. Furthermore, a molecular docking study indicated that the compounds 20–25 binding to the topo II-α are able to interact with the same binding site as the anticancer drug etoposide, suggesting that the ureas could inhibit the enzyme by the same mechanism of action observed for etoposide, which prevents re-ligation of the DNA strands.
Keywords: ureas; solvent-free synthesis; DNA-topoisomerase; molecular docking
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Esteves-Souza, A.; Rodrigues-Santos, C.E.; Del Cistia, C.N.; Silva, D.R.; Sant'Anna, C.M.R.; Echevarria, A. Solvent-Free Synthesis, DNA-Topoisomerase II Activity and Molecular Docking Study of New Asymmetrically N,N'-Substituted Ureas. Molecules 2012, 17, 12882-12894.
Esteves-Souza A, Rodrigues-Santos CE, Del Cistia CN, Silva DR, Sant'Anna CMR, Echevarria A. Solvent-Free Synthesis, DNA-Topoisomerase II Activity and Molecular Docking Study of New Asymmetrically N,N'-Substituted Ureas. Molecules. 2012; 17(11):12882-12894.
Esteves-Souza, Andressa; Rodrigues-Santos, Claudio E.; Del Cistia, Catarina N.; Silva, Daniel R.; Sant'Anna, Carlos M.R.; Echevarria, Aurea. 2012. "Solvent-Free Synthesis, DNA-Topoisomerase II Activity and Molecular Docking Study of New Asymmetrically N,N'-Substituted Ureas." Molecules 17, no. 11: 12882-12894.