Thirty Years Seeking Drugs for Chagas Disease
Abstract: Chagas disease, or American trypanosomiasis, an untreating parasitic disease that affect near to 6-7 million people worldwide. The illness is confined mainly in rural areas of 21 Latin American countries (excluding the Caribbean islands). Due to population mobility, most infected people live in urban settings and the infection has been increasingly detected in many European and some African, Eastern Mediterranean and Western Pacific countries, the United States of America and Canada. The current treatment relies on two old and non-specific chemotherapeutic agents, Nifurtimox and Benznidazole. Despite the major advances that have been made in the identification of specific targets that afford selectivity, the drugs used today have serious side effects. Furthermore, differences in drug susceptibility among different protozoan (T. cruzi) isolates have led to varied parasitological cure rates depending on the geographical region. There is, therefore, an urgent need for the development of new antichagasic drugs. In this regard we have spent near to three decades in the search for more effective agents able to compromise the proliferation of T. cruzi. We stated our research with agents that trigger oxidative stress intraparasitically and then continued with compounds that could selectively inhibit parasite-targets. We systematically characterized representatives of a wide range of different chemical families. Here I summarize our ongoing efforts to identify potential anti-T. cruzi agents discussing and presenting the structure-activity relationship observed among the different groups of chemical families.