Summary:
Topoisomerases take an active part at replication, transcription and chromatin
condensation of DNA. Their activity is based on the break of DNA double helix
(single strand break from topoisomerase I or double strand break from
topoisomerase II) by creating a transient enzyme-DNA complex. The topoisomerase
inhibitors act by stabilizing this complex, which causes irreversible breakage
of the double helix of DNA, thereby leading to apoptosis of tumor cells. Among
different classes of topoisomerase inhibitors, PZA and DACA have been
extensively studied and were also used as lead compounds for the development of
structurally related analogues. Much effort has been devoted to the
modification of the chromophore in order to optimize its characteristics,
regarding severe side effects and solubility under physiological conditions,
resulting in the development of a number of aminosubstituted acridine
derivatives. Prompted by the above mentioned studies we present here the
synthesis of some novel aza-acridone aminosubstituted compounds. Our aim is to
understand the structure–activity relationships regarding the impact of the
fused nitrogen in the acridone core, the impact of the nitro, the
aminosubstituted side chain and the α,β unsaturated group.
Keywords:
Cancer, Inhibitors, Topoisomerase, Pyrazoloacridine, Aminoacridines
