Recent Advances in Electrochemical Biosensors Based on Enzyme Inhibition for Clinical and Pharmaceutical Applications

Abstract

A large number of enzyme inhibitors are used as drugs to treat several diseases such as gout, diabetes, AIDS, depression, Parkinson's and Alzheimer's diseases. Electrochemical biosensors based on enzyme inhibition are useful devices for an easy, fast and environment friendly monitoring of inhibitors like drugs. In the last decades, electrochemical biosensors have shown great potentials in the detection of different drugs like neostigmine, ketoconazole, donepezil, allopurinol and many others. They attracted increasing attention due to the advantage of being high sensitive and accurate analytical tools, able to reach low detection limits and the possibility to be performed on real samples. This review will spotlight the research conducted in the past 10 years (2007-2017) on inhibition based enzymatic electrochemical biosensors for the analysis of different drugs. New assays based on novel bio-devices will be debated. Moreover, the exploration of the recent graphical approach in diagnosis of reversible and irreversible inhibition mechanism will be discussed. The accurate and the fast diagnosis of inhibition type will help researchers in further drug design improvements and the identification of new molecules that will serve as new enzyme targets.

Keywords: diagnosis of inhibition; disease; drug; electrochemical biosensors; enzyme inhibition.

Figure 1

Relationship between in silico prediction and new analytical tools and their importance in drug therapy as preliminary assays before proceeding to in vivo tests.

Scheme 1

Kinetics of non-inhibitive enzymatic reaction (A), irreversible enzyme inhibition (B) and reversible enzyme inhibition (C).

Figure 2

Degree of inhibition determination using enzyme-based electrochemical biosensor.

Figure 3

Effect of incubation time (A) and enzyme concentration (B) on $I_{50}$ in the case of irreversible inhibition.

Figure 4

Variation of $I_{50}$ in function of time in case of irreversible inhibition. The curve was plotted using the equation of $I_{50}=\raisebox{1ex}{$0.69\times K_i$}\!\left/ \!\raisebox{-1ex}{$\left(\left(K_{inac}\times t\right)+0.69\right)$}\right.$ and the following parameters were used: $K_i=0.84 \mathsf{\mu }\mathrm{M}$, $K_{inac}=0.25 {\min }^{-1}$.

Figure 5

Effect of concentration of substrate on $I_{50}$ in case of reversible inhibition (curve a) competitive, (curve b) non-competitive and (curve c) uncompetitive.

Figure 6

Schematic presentation of different biosensors based on numerous bio-recognition elements.