The Role of DNA Intercalators and Acridine Derivatives in Cancer Chemotherapy

Abstract

Cancer is characterized by the accumulation of Deoxyribonucleic Acid (DNA) damage; consequently, drugs used in cancer therapy target DNA and interact with nucleic acids through covalent bonding, groove binding, electrostatic interactions, and intercalation. Therefore, this review encompasses a bibliographic survey of the historical, structural, and functional aspects of DNA, the main characteristics of carcinogenesis, and how medicines interact with DNA, especially acridine and its derivatives. Among the factors that contribute to cancer are physical, chemical, and biological factors. Most DNA damage caused by these factors can be corrected by repair enzymes; however, when these enzymes fail to fully correct the damage, permanent point mutations may result. Modern approaches to drug discovery have focused their studies on understanding how the interaction with the target site occurs. In this context, intercalation is the insertion of planar molecules, intercalators, between the base pairs of the double helix. These compounds are stabilized by π-π interactions and hydrogen bonds, causing conformational changes, hardening of the DNA, and interruption of the cell cycle. Among the classes of intercalators, acridine and its derivatives stand out, which have excellent anticancer properties. Finally, it is hoped that this review will enhance understanding of DNA, drug-DNA interactions, acridine and its main derivatives, and provide a solid foundation for students and researchers who want to study the topic of cancer.