Development of Tdp1 inhibitors based on natural biologically active compounds as prototypes of antitumor drugs

Abstract

Key words: tyrosyl-dNAphosphodiesterase I, inhibitor of tyrosyl-dNA phosphodiesterase I Motivation and Aim: developing inhibitors for dNA repair enzymes is a promising approach to improve anticancer therapy, in particular for drug-resistant tumors. tdp1 plays a key role in the repair of top1-dNA covalent complexes formed by topoisomerase-1 (top1) poisons such as drugs of the camptothecin group, which makes it a promising target in the treatment of cancer [1]. the development of new inhibitors of dNA repair enzymes based on natural compounds and their derivatives is particularly relevant, since such compounds often have complementarity to targets of biological origin and possess broad range of biological activities. Methods and Algorithms: Screening of compounds -potential inhibitors is carried out using a real-time fluorescence measurement method, which makes it possible to determine the initial reaction rate with high accuracy [2]. the effect of the selected compounds on the proliferation of transplanted tumor cell lines and the evaluation of cell death are studied using the mtt test. We used derivatives of usnic acid, coumarin and