Background: Inhibition of the DNA repair enzyme, tyrosyl-DNA phosphodiesterase 1
(TDP1), may increase the efficacy of cancer drugs that cause damage to tumor cell DNA. Among
the known TDP1 inhibitors, there are compounds containing moieties of natural substances, e.g.,
monoterpenoids. In this work, we synthesized several compounds containing aromatic/
heteroaromatic amines and monoterpenoid groups and assessed their TDP1 inhibition potential.
Methods: Structures of all the synthesized compounds were confirmed by 1H and 13C NMR as well
as HRMS. The TDP1 inhibitory activity of the amines was determined by real-time fluorescence
Results: The synthesized secondary amines had TDP1 inhibitory activity IC50 in the range of 0.79–
9.2 μM. The highest activity was found for (–)-myrtenal derivatives containing p-bromoaniline or
Conclusion: We synthesized 22 secondary amines; of these, 17 amines are novel chemical structures.
Many of the amines inhibit TDP1 activity in the low micromolar range. Therefore, these
compounds are promising for further study of their antiproliferative activity in conjunction with
DNA damaging drugs.