Natural Product Inhibitors of Topoisomerases: Review and Docking Study

Abstract

Since ancient times, natural products have been used in treating various diseases effectively and safely. Nowadays, these natural compounds are submitted to sophisticated methodologies from isolation, computing, analytical, and even serving as pharmacophore suggestions for synthesis. The substances extracted from marine species, plants, and microorganisms present activities beneficial to our health, including protection against malignant tumors. The topoisomerase enzymes play an important role in DNA metabolism, and searching for enzyme inhibitors is an important target in the search for new anticancer drugs. This review discusses this problem, reporting research involving alkaloids, terpenes, flavonoids, xanthones, coumarins, acetogenins, and in addition, includes a docking study with our Brazilian diterpenes to topoisomerases I and II. The better compound, the trachylobane 1, forms one hydrogen bond when submitted to docking with Topo I (with the ASP533 residue) and two with residues in Topo II (THR213 and TYR188). The difference observed in the energy of formation can be attributed to hydrogen-bond interactions. The difference observed in the energy of formation can be attributed to hydrogen-bond interactions.

Keywords: Alkaloids; cancer; docking; flavonoids; terpenes; topoisomerases.