Molecular And Structural Basis Of Dnabinding Anticancer Drug Action

Anticancer drugs targeted to DNA bind to the same by either non-covalent forces or covalent interactions. The primary and most important step in the functioning of a DNA targeting drug is the base-specific recognition of DNA by the drug. This initial process of recognition is driven by size and shape complementarities between the drug and its DNA - binding site. Non-covalent forces such as the coulombic force, van der Waals interactions, hydrogen bonding and stacking interaction stabilize the primary complex formed. For drugs that interact with DNA via non-covalent forces, the active primary complex is responsible for its intracellular function; whereas, for drugs that interact with DNA via covalent forces, the covalent bond formation is preceded by the non-covalent reversible drug-DNA association that determines the specificity, because it positions the reactive part of the drug along the target site in the DNA. The general mechanism of action of DNA targeting anti-cancer drugs is shown below:

Covalently Interacting drugs

cleaved DNA/ covalent adducts/ cross-linked

Non-covalently interacting drugs products

Chemical basis of action for DNA targeting anti-cancer drugs

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