REVIEW: PRODRUG CONCEPT IN DRUG DESIGN

In the world of drug discovery and development, prodrugs have become an established tool for improving physicochemical, biopharmaceutical or pharmacokinetic properties of pharmacologically active agents. Prodrugs are bio reversible derivatives of drug molecules that undergo an enzymatic and/or chemical transformation in vivo to release the active parent drug, which can then exert the desired pharmacological effect. The basic aim of prodrug design is to overcome undesirable drug properties, such as low solubility in water or lipid membranes, low target selectivity, chemical instability, undesirable taste, irritation or pain after local administration, presystolic metabolism and toxicity. In fact, about 10% of the drugs approved worldwide can be classified as prodrugs. Although the development of a prodrug can be very challenging, the prodrug approach represents a feasible way to improve the undesirable properties of investigational drugs or drugs already on the market. In this article, the concepts of prodrug and the classifications of prodrugs will be offered. Furthermore, this article describes the basic functional groups that are amenable to prodrug design and highlights the major applications of the prodrug strategy.