Inhibition of the DNA Repair Enzyme TDP1 by the Resin Acid Derivatives As a New Way to Increase the Efficiency of Glioblastoma Chemotherapy

A new class of tyrosyl-DNA phosphodiesterase 1 (TDP1) inhibitors has been found among resin acid derivatives. Several novel bisureas derived from dehydroabietylamine (DHAm) were synthesized and tested for TDP1 inhibition. The synthesized compounds showed IC50 values in the range of 0.09 to 0.19 µM. Several compounds demonstrated the enhancement of cytotoxic activity of the alkylating agent, Lomustine, the chemotherapeutic drug used for the glioblastoma (GBM) treatment. The effect has been studied in two GBM cell lines U-87 and SNB19.