Interactions between DNA and the acridine intercalator: A computational study

Comput Biol Chem. 2024 Feb 12;109:108029. doi: 10.1016/j.compbiolchem.2024.108029. Online ahead of print.ABSTRACTCancer is a global public health problem characterized by deviations in the mechanisms that control cell proliferation, resulting in mutations and variations in the structure of DNA. The mechanisms of action of chemotherapeutic drugs are related to their interactions and binding with DNA; consequently, the development of antineoplastic agents that target DNA has extensively focused on use of acridine, a heterocyclic molecule that binds to deoxyribonucleic acid via intercalation, a process that modifies DNA and makes replication impossible. In this context, this study aimed to computationally investigate how acridine intercalators interact with DNA by evaluating the mechanism of interactions, binding, and interaction energies using quantum mechanics calculations. Molecular electrostatic potential (MEP) analysis revealed that acridine has well- distributed negative charges in the center of the molecule, indicative of a dominant electron-rich region. Acridine exhibits well-defined π orbitals (HOMO and LUMO) on the aromatic rings, suggesting that charge transfer occurs within the molecule and may be responsible for the pharmacological activity of the compound. Structural analysis revealed that acridine interacts with DNA mainly through hydrogen bonds between HAcridine… ODNA with bond lengths ranging from 2.370 Å to 3.472 Å. The Binding energy (ΔEBind) showed that...
Source: Computational Biology and Chemistry - Category: Bioinformatics Authors: Source Type: research