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Updated: Jul 24, 2025
Formation of Covalent DNA Adducts by Enzymatically Activated Carcinogens and Drugs In Vitro and Their Determination by 32P-postlabeling
Published on: March 20, 2018
Electrochemical and theoretical study on interaction between erlotinib and DNA
Milan Jovanović1, Katarina Nikolic2, Marija Čarapić3
1University of Belgrade ̶ Faculty of Pharmacy, Department of Pharmaceutical Chemistry, Vojvode Stepe 450, P.O.Box 146, 11221 Belgrade, Serbia; University of Belgrade - "VINČA" Institute of Nuclear Sciences - National Institute of the Republic of Serbia, Department of Molecular Biology and Endocrinology, Mike Petrovića Alasa 12-14, Vinča, 11351 Belgrade, Serbia.
Erlotinib (ERL) electrochemical behavior was studied, revealing its redox mechanisms and DNA binding modes. Electrochemical biosensor results suggest ERL primarily intercalates into DNA, with minor groove binding also occurring.
Area of Science:
- Electrochemistry
- Biochemistry
- Molecular Biology
Background:
- Erlotinib (ERL) is a tyrosine kinase inhibitor with potential DNA-interacting properties.
- Understanding ERL's redox mechanism and DNA binding is crucial for its therapeutic applications.
Purpose of the Study:
- To elucidate the electrochemical behavior and redox mechanism of ERL.
- To determine the mode of interaction between ERL and DNA.
- To quantify the binding affinity of ERL to DNA.
Main Methods:
- Voltammetric techniques (CV, DPV, SWV) were employed to study ERL's electrochemical properties across a pH range.
- A multi-layer ct-DNA electrochemical biosensor was utilized to investigate ERL-DNA interactions.
- Molecular docking and molecular dynamics simulations were performed to predict binding modes.
Main Results:
- ERL exhibits distinct adsorption-controlled oxidation and diffusion-adsorption mixed-controlled reduction processes.
- ERL binding to ct-DNA leads to a decrease in deoxyadenosine peak current, indicating interaction.
- A binding constant of K = 8.25 × 10^4 M^-1 was calculated for ERL-DNA complex.
- Molecular simulations suggest both intercalation and minor groove binding, with intercalation being potentially dominant.
Conclusions:
- The study clarifies the electrochemical redox mechanism of ERL.
- ERL interacts with DNA, with intercalation appearing to be the predominant binding mode.
- These findings provide insights into ERL's molecular interactions with DNA.
