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

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.