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Synthesis, Basicity, Structural Characterization, and Biochemical Properties of Two [(3-Hydroxy-4-pyron-2-yl)methyl]amine Derivatives Showing Antineoplastic Features.

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journal contribution
posted on 02.03.2012, 00:00 by Stefano Amatori, Gianluca Ambrosi, Mirco Fanelli, Mauro Formica, Vieri Fusi, Luca Giorgi, Eleonora Macedi, Mauro Micheloni, Paola Paoli, Roberto Pontellini, Patrizia Rossi
The N,N′-bis­[(3-hydroxy-4-pyron-2-yl)­methyl]-N,N′-dimethylethylendiamine (malten) and 4,10-bis­[(3-hydroxy-4-pyron-2-yl)­methyl]-1,7-dimethyl-1,4,7,10-tetraazacyclododecane (maltonis) were synthesized and characterized. The acid–base behavior, structural characterizations, and biochemical studies in aqueous solution were reported. Each compound contains two 3-hydroxy-2-methyl-4-pyrone units (maltol) symmetrically spaced by a polyamine fragment, the 1,4-dimethylethylendiamine (malten), or the 1,7-dimethyl-1,4,7,10-tetraazacyclododecane (maltonis). They are present at physiological pH 7.4 in the form of differently charged species: neutral but in a zwitterion form for malten and monopositive with an internal separation of charges for maltonis. Malten and maltonis are both able to alter the chromatin structure inducing the covalent binding of genomic DNA with proteins, a feature consistent with the known antiproliferative activity exerted by this class of molecules. Solid-state results and MD simulations in water show that malten, because of its molecular topology, should be more prone than maltonis to act as a donor of H-bonds in intermolecular contacts, thus it should give a better noncovalent approach with the negatively charged DNA. Crystal structures of [H2malten]2+ and [H2maltonis]2+ cations were also reported.