Berberine is known for its wide range of biological activity, including hypolipidemic, antibacterial, hypoglycemic, etc. Our interest is focused on the inhibitory properties of berberine and its derivatives in relation to the DNA reparation enzyme Tdp1. Inhibition of various DNA repair enzymes, including Tdp1, is one of the promising fields in the evolution of antitumor therapy.

We synthesized and tested a number of berberine derivatives, which allowed us to identify leading compounds and understand which functional groups should contain a derivative and in which positions in order to exhibit inhibitory activity. According to SAR data analysis only tetrahydroberberine derivatives containing a reduced ring C show inhibitory activity. The presence of substituents in both positions simultaneously (amide or sulfonate group in 9 and bromine in 12) leads to increasing of inhibitory activity (IC₅₀ = 0.5 – 4 µM) in comparison with unbrominated in 12 position analogues. Almost all of the most active derivatives exhibit low cytotoxicity. Thus, the results reveal that some berberine derivatives are potential agents that can be used in antitumor therapy.

This study was funded by the Russian Science Foundation grantNo19-13-00040