Departamento de Química, Instituto de Ciências Exatas, Universidade Federal Rural do Rio de Janeiro, Seropédica, Rio de Janeiro, Brazil.
Molecules. 2012 Nov 1;17(11):12882-94. doi: 10.3390/molecules171112882.
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.
采用无溶剂条件，从肉桂醛和对取代苯胺衍生的席夫碱出发，制备了一系列新的不对称 N,N'-取代脲 20-25，这是一种环保的方法，随后进行还原反应，得到相应的不对称仲胺。所有的中间体都是采用无溶剂反应制备的，并与传统方法进行了比较。所有的反应都需要极短的时间，与其他方法相比，采用无溶剂条件时，收率较高。在松弛实验中评估了 DNA-拓扑异构酶 II-α（topo II-α）的活性，结果表明，除脲 24 外，所有化合物在 10 μM 时均抑制了酶的活性。此外，分子对接研究表明，化合物 20-25 与 topo II-α的结合能够与抗癌药物依托泊苷的相同结合位点相互作用，这表明脲类可能通过与依托泊苷相同的作用机制抑制酶的活性，从而阻止 DNA 链的重新连接。
