Estudos de docking molecular de derivados da acridina como potenciais intercaladores de DNA e inibidores da topoisomerase IIα

Abstract

Cancer is a disease that affects about 13% of the world's population per year and has many types of treatments. Among these treatments the most used is chemotherapy, which consists in the use of drugs to control the tumor. For this reason, it is necessary to study new drugs with antitumor activities in order to improve therapy, since current methods still cause many adverse effects. Thus, our objective was to evaluate through molecular docking studies the mechanism of action of acridine derivatives that have known antitumor activity, such as potential DNA intercalators and topoisomerase IIα inhibitors, as well as their pharmacokinetic properties. Thus, eight molecules from an in vitro study were selected, which showed good experimental results against seven tumor types, namely: Breast (MCF-7), liver (HEP-2), colo (COLO-205), (502713), (HCT-15), lung (A-549) and neuroblastoma (IMR-32). These coincided with the in silico results of the present study, where for the three receptor types, binding energies in the range of -8.25 kcal·mol-1 to -10.68 kcal·mol-1 were obtained, making it clear that these compounds may act as intercalating agents. Thus, one can state that the results of the docking study and the pharmacokinetic properties indicate that there is a formation of stable complexes of acridine derivatives with the receptors, showing potentials for topoisomerase IIα inhibition by poisoning. This suggests that the mechanisms used in this study are plausible and these compounds have promising properties as an antitumoral agents.