A new class of tyrosyl-DNA phosphodiesterase 1 (TDP1) inhibitors based on disaccharide nucleosides was identified. TDP1 plays an essential role in the resistance of cancer cells to currently used antitumour drugs based on Top1 inhibitors such as topotecan and irinotecan. The most effective inhibitors investigated in this study have IC50 values (half-maximal inhibitory concentration) in 0.4–18.5 µM range and demonstrate relatively low own cytotoxicity along with significant synergistic effect in combination with anti-cancer drug topotecan. Moreover, kinetic parameters of the enzymatic reaction and fluorescence anisotropy were measured using different types of DNA-biosensors to give a sufficient insight into the mechanism of inhibitor’s action.

Existing lignocellulosic biomass fractionation processes produce lignin with random, interunit C–C bonds that inhibit its depolymerization and constrain its use. Here, we exploit the aldehyde stabilization of lignin to tailor...

Demand for sustainable polar aprotic solvents is increasing due to their unique solubilizing properties and the toxicity of conventional analogs, which are facing pressure from extensive safety legislation. Polar aprotic...