Background: DNA topoisomerase II-α (Top2-α), an essential enzyme for the management
of DNA during replication, transcription, recombination, and chromatin remodeling, is one of
the most important anticancer targets. Numerous molecules have been designed as Top2-α inhibitors.
However, several studies have shown that polymorphisms and mutations in Top2 have conferred
resistance to most of these anticancer drugs. The aim of this study was to computationally examine
the mechanisms by which genomic variations in Top2-α could affect its resistance to Amsacrine
and Mitoxantrone as important inhibitors of the enzyme.
Results: The results showed that variants K529E, R568H, R568G and T530M could affect Top2-α
inhibition by Amsacrine causing possible drug-resistant. Moreover, R487K, and Y481C variants
could change the response of the enzyme to Mitoxantrone.
Conclusion: These results could facilitate the prediction and development of more effective drugs
for Top2-α variants, making the cancer chemotherapy more effectiv