Recently, World Health Organization (WHO) and Medicins San Frontieres (MSF) proposed a classification of diseases as global, neglected and extremely neglected. Global diseases, such as
cancer, cardiovascular and mental (
CNS) diseases represent the targets of the majority of the R&D efforts of
pharmaceutical companies.
Neglected diseases affect millions of people in the world yet existing
drug therapy is limited and often inappropriate. Furthermore, extremely
neglected diseases affect people living under miserable conditions who barely have access to the bare necessities for survival. Most of these diseases are excluded from the goals of the R&D programs in the pharmaceutical industry and therefore fall outside the
pharmaceutical market. About 14 million people,mainly in developing countries, die each year from
infectious diseases. From 1975 to 1999,1393 new drugs were approved yet only 1% were for the treatment of
neglected diseases[3]. These numbers have not changed until now, so in those countries there is an urgent need for the design and synthesis of new drugs and in this area the
prodrug approach is a very interesting field. It provides, among other effects, activity improvements and toxicity decreases for current and new drugs, improving market availability. It is worth noting that it is essential in
drug design to save time and money, and
prodrug approaches can be considered of high interest in this respect. The present review covers 20 years of research on the design of
prodrugs for the treatment of neglected and extremely
neglected diseases such as
Chagas' disease (
American trypanosomiasis),
sleeping sickness (African trypanosomiasis),
malaria,
sickle cell disease,
tuberculosis,
leishmaniasis and
schistosomiasis.