Prodrugs targeting the central nervous system (cns)
Date
2015-08-07
Authors
Salameh, Falasteen
Karaman, Donia
Karaman, Rafik
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Abstract
The classical approach for delivery of drugs into the central nervous
system (CNS) is associated with adverse effects and it has many
limitations. Therefore, extensive efforts have been done in searching
and developing novel methods for achieving such delivery. This minireview
discusses the design and synthesis of selected targeting
prodrugs for the treatment of conditions related to impairment in the
CNS such as Parkinson‘s and Alzheimer‘s diseases. Such approaches
include targeting prodrugs which are designed to interact with unique
cellular conditions at the target site, especially the availability of
certain enzymes and transporters at these sites. In addition, part of this
mini-review is devoted to prodrugs design based on enzyme models
that have been invoked to understand how enzymes
catalyzebiotransformation. In this approach, the prodrugs design isdone using quantum
molecular orbital and molecular mechanics methods. The equations obtained from
correlations of experimental and calculated rate values for some intramolecular processes are
used to predict parameters for other intramolecular processes that can be utilized as prodrugs
linkers. In this approach, there is no need for enzymes to catalyze the conversion of the
prodrug to its active parent drug and the conversion rate of the prodrug is dependent only on
those factors playing dominant role in the rate-limiting step of the process.
Description
Keywords
Prodrugs , Targeted prodrugs , CNS , Parkinson‘s disease , Dopamine , Alzheimer‘s disease , Intramolecularity , Enzyme models