Prodrugs-Current and Future Drug Development Strategy

Abstract

The focus of traditional prodrug approach was on altering various physiochemical parameters, whereas the current modern computational approach considers designing prodrugs through attaching appropriate linkers with drugs having poor bioavailability which upon exposure to physiological environments release the parent active drugs in a programmable (controlled) manner resulting in an improvement of their bioavailability. With the possibility of designing prodrugs with different linkers, the release rate of the parent active drugs can be controlled. The future of prodrug technology is exciting and yet challenging. Advances must be made in understanding the chemistry of many organic reactions that can be effectively utilized to enable the development of more types of prodrugs. The understanding of organic reaction mechanisms of certain processes, particularly intramolecular reactions, will be the next major milestone in this field. It is envisioned that the future of prodrug technology holds the ability to create safe and efficacious delivery of a wide range of active small molecules and biotherapeutics. This goal can be achieved using computational chemistry methods such as ab initio, semi-empirical and density functional theory (DFT), and molecular mechanics (MM) to calculate physicochemical and molecular properties of current marketed drugs suffer low bioavailability or/and unpleasant taste or odor.