Abstract

ANTICANCER PRODRUGS - THREE DECADES OF DESIGN

Waad Horani, Ameen Thawabteh, Laura Scrano, Sabino A. Bufo, Gennaro Mecca, Rafik Karaman*

ABSTRACT

The conventional old treatment method for cancer therapy is associated with severe side effects along with several limitations. Therefore, searching and developing new methods for cancer became crucial. This mini review was devoted on the design and synthesis of prodrugs for cancer treatment. The methods discussed include targeted prodrugs which are depending on the presence of unique cellular conditions at the desired target, especially the availability of certain enzymes and transporters at these target sites, antibody directed enzyme prodrug therapy (ADEPT), gene-directed enzyme prodrug therapy (GDEPT) which is considered one of the important strategies for the treatment of cancer and prodrugs based on enzyme models that have been advocated to understand enzyme catalysis. In this approach, a design of prodrugs is accomplished using computational calculations based on molecular orbital and molecular mechanics methods. Correlations between experimental and calculated rate values for some intramolecular processes provided a tool to predict thermodynamic and kinetic parameters for intramolecular processes that can be utilized as prodrugs linkers. This approach does not require any enzyme to catalyze the prodrug interconversion. The interconversion rate is solely dependent on the factors govern the limiting step of the intramolecular process.

Keywords: prodrugs, Targeted prodrugs, ADEPT, GDEPT, Cancer, Intramolecular process, Enzyme models.