Human topoisomerase IB is an important target in cancer therapy and drugs selectively stabilizing
the topoisomerase IB-DNA covalent complex are in clinical use for several cancer types. Tyrosyl-
DNA phosphodiesterase 1 is involved in the DNA repair resolving the topoisomerase IB-DNA covalent
complex that is extremely dangerous for the survival of the cells since it produces an irreversible DNA
damage. Given the close biological relationship between these two enzymes, the development of synergistic
inhibitors, called dual-inhibitors, is an important challenge in cancer therapy and computer-aided
drug design may help in the identification of the best compounds. In this review, an overview of the
compounds inhibiting one of the two enzymes or acting as dual inhibitors is provided. Moreover, the
general procedures of the virtual screening approach, providing a description of two widely used opensource
programs, namely AutoDock4 and AutoDock Vina, are described. Finally, an application of the
two programs on a selected number of dual inhibitors for tyrosyl-DNA phosphodiesterase 1 and topoisomerase
IB and their performance is briefly discussed.
Keywords: AutoDock4, autodock vina, dual-inhibitors, indenoisoquinolines, molecular docking, topoisomerase IB, tyrosyl-
DNA phosphodiesterase, virtual screening.
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