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Prodrugs for the Treatment of Neglected Diseases
Lapdesf - Laboratório de Desenvolvimento de Fármacos, Departamento de Fármacos e Medicamentos, Faculdade de Ciências Farmacêuticas - UNESP Rodovia Araraquara-Jaú Km 1, 14801-902, Brazil
LAPEN – Laboratório de Planejamento e Síntese de Quimioterápicos Potencialmente Ativos em Endemias Tropicais, Departamento de Farmácia, Faculdade de Ciências Farmacêuticas – USP/SP, R. Prof. Lineu Prestes, 580, B-13S,Cidade Universitária,Brazil
* Authors to whom correspondence should be addressed.
Received: 11 January 2008; in revised form: 12 March 2008 / Accepted: 12 March 2008 / Published: 19 March 2008
(This article belongs to the Special Issue Prodrugs
Abstract: 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 . 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.
Keywords: Tropical neglected diseases; Prodrug design; American trypanosomisasis; African trypanosomiasis; Malaria; Sickle cell disease; Tuberculosis; Leishmaniasis; Schistosomiasis.
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Chung, M.C.; Ferreira, E.I.; Santos, J.L.; Giarolla, J.; Rando, D.G.; Almeida, A.E.; Bosquesi, P.L.; Menegon, R.F.; Blau, L. Prodrugs for the Treatment of Neglected Diseases. Molecules 2008, 13, 616-677.
Chung MC, Ferreira EI, Santos JL, Giarolla J, Rando DG, Almeida AE, Bosquesi PL, Menegon RF, Blau L. Prodrugs for the Treatment of Neglected Diseases. Molecules. 2008; 13(3):616-677.
Chung, Man C.; Ferreira, Elizabeth I.; Santos, Jean L.; Giarolla, Jeanine; Rando, Daniela G.; Almeida, Adélia E.; Bosquesi, Priscila L.; Menegon, Renato F.; Blau, Lorena. 2008. "Prodrugs for the Treatment of Neglected Diseases." Molecules 13, no. 3: 616-677.