- Guanidinium-based derivatives: Searching for new kinase inhibitors
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Considering the structural similarities between the kinase inhibitor sorafenib and 4,4′-bis-guanidinium derivatives previously prepared by Rozas and co., which display interesting cytotoxicity in cancer cells, we have studied whether this activity could result from kinase inhibition. Five new families have been prepared consisting of unsubstituted and aryl-substituted 3,4′-bis-guanidiniums, 3,4′-bis-2-aminoimidazolinium and 3-acetamide-4′-(4-chloro-3-trifluoromethylphenyl)guanidinium derivatives. Cytotoxicity (measuring the IC50 values) and apoptosis studies in human HL-60 promyelocytic leukemia cells were carried out for these compounds. Additionally, their potential inhibitory effect was explored on a panel of kinases known to be involved in apoptotic pathways. The previously prepared cytotoxic 4,4′-bis-guanidiniums did not inhibit any of these kinases; however, some of the novel 3,4′-substituted derivatives showed a high percentage inhibition of RAF-1/MEK-1, for which the potential mode of binding was evaluated by docking studies. The interesting antitumour properties showed by these compounds open up new exciting lines of investigation for kinase inhibitors as anticancer agents and also highlights the relevance of the guanidinium moiety for protein kinase inhibitors chemical design.
- Diez-Cecilia, Elena,Kelly, Brendan,Perez, Concepcion,Zisterer, Daniela M.,Nevin, Daniel K.,Lloyd, David G.,Rozas, Isabel
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p. 427 - 441
(2014/06/09)
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- One-step double reduction of aryl nitro and carbonyl groups using hydrazine
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Single-step reduction of aryl nitro and carbonyl groups to the corresponding synthetically useful alkyl-anilines occurs with excellent yields by treatment with hydrazine and a base in a solvent-free reaction. The method has been applied to a broad range of compounds with different properties. Investigations into the mechanism of the reduction reveal that each group is reduced independently. A mechanism is proposed for this novel reduction of aromatic nitro groups.
- Diez-Cecilia, Elena,Kelly, Brendan,Rozas, Isabel
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supporting information; experimental part
p. 6702 - 6704
(2012/01/05)
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