DNA binding and Topoisomerase inhibition: How can these mechanisms be explored to design more specific anticancer agents?

• Published in: Biomedicine & pharmacotherapy Vol. 96; pp. 1538 - 1556
• Main Authors: de Almeida, Sinara Mônica Vitalino, Ribeiro, Amélia Galdino, de Lima Silva, Geilza Carla, Ferreira Alves, Josival Emanuel, Beltrão, Eduardo Isidoro Carneiro, de Oliveira, Jamerson Ferreira, de Carvalho, Luiz Bezerra, Alves de Lima, Maria do Carmo
• Format: Journal Article
• Language: English
• Published: France Elsevier Masson SAS 01.12.2017
• Subjects: Acridine derivatives; Animals; Antineoplastic Agents - pharmacology; Antineoplastic Agents - therapeutic use; DNA - metabolism; DNA Topoisomerases - metabolism; DNA-topoisomerase; Drug Design; Humans; Metallic compounds; Nitrogenous heterocyclic derivatives; Thiosemicarbazone; Topoisomerase Inhibitors - pharmacology; Topoisomerase Inhibitors - therapeutic use; Metallic compounds; Thiosemicarbazone; Acridine derivatives; Nitrogenous heterocyclic derivatives; DNA-topoisomerase
• ISSN: 0753-3322; 1950-6007
• DOI: 10.1016/j.biopha.2017.11.054

DNA is considered one of the most promising targets of molecules with anticancer activity potential. Its key role in various cell division mechanisms, which commands the intense multiplication of tumor cells, is considered in studies with compounds whose mechanisms of action suggest likeliness of interaction. In addition, inhibition of enzymes that actively participate in biological functions of cells such as Topoisomerase, is seen as a primary factor for conducting several events that result in cell death. Discovery of new anticancer chemotherapeutical capable of interacting with DNA and inhibiting Topoisomerase enzymes is highlighted in anticancer research. The present review aims at showing through distinct biological tests the performance of different candidates to anticancer drugs and their respective chemical modifications, which are crucial and/or determinant for DNA affinity and inhibition of important enzymes in cells’ vital processe to either separately or synergistically optimize anticancer activity.