The Inhibition of Topoisomerase II? with (1E,4E)-1,7-Bis(4-hydroxyphenyl)Hepta-1,4-Dien-3-One)-Based Natural Products

DNA Topoisomerase enzymes are found in throughout all life on earth and are an essential part of DNA strand management of living beings. This unwinding is essential to ensuring continuous DNA replication of the strand, which cannot occur if one of the following is restricting said DNA replication. Seeing as these enzymes play a crucial role in a DNA’s continuance, inhibiting cellular/DNA replication in cancer cells while limiting other cellular exposure has been a drive for finding chemicals that can properly dock and prevent the function of topoisomerase enzymes. This project served to use build from naturally occurring inhibitors of topoisomerase II α, optimize their physiochemical properties, evaluate their simulated chemical docking in topoisomerase II α enzymes, synthesis target the target molecule, and test their ability to inhibit topoisomerase II α. Current synthesis targets are based on a natural product isolated from mistletoe, (1E,4E)-1,7-bis(4-hydroxyphenyl)hepta-1,4-dien-3-one. This natural product was evaluated for its interactions with topoisomerase II α using the MOE-2020 computational suite. A series of candidates was evaluated and the best binding of them was undertaken as a synthetic target. Here we report on the design and synthesis of these candidates in advance of their testing.