Study of Anticancer Drugs Interaction with Hemoglobin by Electrochemical Methods and Molecular Docking: Implications towards Anticancer Treatment

Abstract

Chemotherapeutic drugs tend to cause hemolysis; however, hemoglobin's mode of action is still less explored. In the present study, we used electrochemical methods and molecular docking approach to study anticancer drugs and hemoglobin interaction. For this purpose, we prepared self-assembled monolayers (SAMs) of thiolated hemoglobin on the gold substrate. Electrochemically active chemo drugs, i. e., doxorubicin, withaferin-a, and 5-fluorouracil, are selected and allowed to interact with SAMs of hemoglobin at the physiological condition to study the redox activity and impedimetric behavior. Doxorubicin and withaferin-a show similar behavior in cyclic voltammetry and impedance spectroscopic, i. e., redox process due to hydroquinone/quinone/ketone ring, and faster interfacial electro-transfer kinetics and decreasing in electrontransfer resistance with increasing concentration. In contrast, 5fluorouracil shows only the oxidation reaction. The molecular docking studies were in good agreement with the electrochemical study. All selected anticancer drugs are found to bind hemoglobin, with doxorubicin showing maximum binding efficiency and 5-fluorouracil showing the least. Doxorubicin's highest binding sites contain Tyr 145, which may be involved in the electron transport pathway between doxorubicin and hemoglobin, while Tyr35 in withaferin-a, but absent in case of 5-fluorouracil.

The Experimental Design Approach in Square‐Wave Voltammetric Determination of Tamoxifen by NiO‐CPE**

“…Thus, they appear to have a high electrochemical signal due to the electro-oxidation of such functional groups or oxidative cyclization reactions. [48][49][50][51][52][53][54] The semiconductor nickel oxide with a crystal defect band gap of about 3.6-4 eV is a chemical stable with a great isoelectric point (IEP) that has been an exciting modifier for the electrode surface because of its higher catalytic activity for the oxidation of many organic compounds. It also has high electrical conductivity, a distinctly electro-active future, and a highly effective surface area.…”

“…Among the chemical compounds, anticancer drugs are highly electroactive due to their structural OH and NH2 functional groups. Thus, they appear to have a high electrochemical signal due to the electro‐oxidation of such functional groups or oxidative cyclization reactions [48–54] …”