Synthesis of New Usnic Acid Derivatives with a Thiadiazine Substituent as Inhibitors of Tyrosyl–DNA–Phosphodiesterase 1
摘要
The interaction of 14-bromousnic acid with hydrazine dithiocarbamate is investigated. The reaction is found to proceed in two parallel paths: with modifying the bromoacetyl group into the 1,3,4-thiadiazine ring and the triketone fragment of the C ring into the pyrazole ring annelated to positions 1,2 or to 2,3 of the dibenzofuran core. Conditions are determined for the selective formation of one of the regioisomers in the structure of which the pyrazole ring is annelated to positions 1,2. It is revealed that this compound inhibits the activity of human DNA repair enzyme tyrosyl–DNA–phosphodiesterase 1 (TDP1) with a half-maximal inhibitory concentration of 1.25 µM, which enables its consideration as the basis for the synthesis of effective inhibitors of this enzyme - components of the antitumor drug.