A novel mechanism was developed to study the interaction of mussel inspired polydopamine surfaces with bovine serum albumin using electrochemical impedance spectroscopy.
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.
β-Cyclodextrin (β-CD)
is the potential drug carrier
to deliver antitumor drugs like doxorubicin (DOX). However, the mechanism
for the inclusion complex formation is still unclear and needs to
be explored. This study investigated the effect of pH on the inclusion
of DOX into thiolated β-CD (β-CD-SH) by electrochemical
and molecular dynamics (MD) simulation. The electrochemical study
shows a clear difference at different pH values. The redox peak due
to the DOX is strongly influenced by pH. At neutral pH, the peak intensity
decreases with time, while slight variation is observed at acidic
and basic pH, depicting the association of DOX to the β-CD-SH
cavity at neutral pH. Also, due to the association, the charge transfer
resistance variation increased with time at neutral pH and decreased
at basic and acidic pH. The electrochemical study was further supported
by MD simulation, suggesting that the cyclodextrin (CD) ring gets
slightly elongated due to the flipping of glucose units, specifically
at neutral pH leading to a strong association. Also, another significant
result observed that the DOX forms an inclusion complex with β-CD-SH
in quinol conformation, not in quinone. Briefly, the study provides
the necessary molecular binding information for designing an effective
β-CD-based targeted drug delivery system.
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