Heterocyclic analogs of 5,12-naphthacenequinone 16*. Synthesis and properties of new DNA ligands based on 4,11-diaminoanthra[2,3-b]thiophene-5,10-dione

A divergent route for the synthesis of new derivatives of 4,11-diaminoanthra[2,3-b]thiophene-5,10-dione was developed based on the introduction of cyclic amines to the terminal positions of 4,11-aminoalkyl groups. Modification of the side chains of anthra[2,3-b]-thiophene-5,10-dione increases the affinity of ligands to DNA duplex and decreases the affinity to G-quadruplexes. An analysis of the structure–activity relationship showed that 2-(piperidin-1-yl)ethylamine is the most promising side chain fragment for the development of new double-stranded DNA ligands. The ability of new ligands to bind to DNA duplex correlates with inhibition of tumor cell growth, which indicates the prospects for a further search for new antitumor compounds or chemical probes for duplex-forming nucleic acid sequences among 4,11-diaminoanthra[2,3-b]thiophene-5,10-diones.