Background:

Nitracrine is an antitumor drug that has been used clinically for several years.

It is demonstrated during the reduction of ledakrin that a key metabolite, a compound with anadditional five-membered ring attaching to positions 1 and 9 of the acridine core and with the retained 9-aminoalkyl side chain, is formed in all the systems that are studied. It is determined that the reactive nitrogen atoms of this additional ring undergo further transformations resulting in the formation of a six-membered ring produced by the addition of a carbon atom to the dihydropyrazoloacridine ring. Furthermore, it is observed that positions 2 and 4 of ledakrin’s acridine ring are susceptible to nucleophilic substitution as revealing by the studies with dithiothreitol. Additionally, although most products from the reduction of ledakrin are extremely unstable, 1-aminoacridinone, producing enzymatically and with dithiothreitol, exhibiting persistent stability under the studied conditions[1].

[1]. Gorlewska K, et al. Products of metabolic activation of the antitumor drug ledakrin (nitracrine) in vitro.