Abstract
Neglected tropical diseases such as Chagas disease and leishmaniasis affect millions of people around the world. Both diseases affect various parts of the globe and drugs traditionally used in therapy against these diseases have limitations, especially with regard to low efficacy and high toxicity. In this context, the class of bisphosphonate-based compounds has made significant advances regarding the chemical synthesis process as well as the pharmacological properties attributed to these compounds. Among this spectrum of pharmacological activity, bisphosphonate compounds with antiparasitic activity stand out, especially in the treatment of Chagas disease and leishmaniasis caused by Trypanosoma cruzi and Leishmania spp., respectively. Some bisphosphonate compounds can inhibit the mevalonate pathway, an essential metabolic pathway, by interfering with the synthesis of ergosterol, a sterol responsible for the growth and viability of these parasites. Therefore, this review aims to present the information about the importance of these compounds as antiparasitic agents and as potential new drugs to treat Chagas disease and leishmaniasis.
Highlights
IntroductionNeglected tropical diseases (NTDs) are responsible for serious public health problems in much of the world, in developing countries located in Latin America, Africa, and Asia, and can affect non-endemic developed regions, such as North America and Europe, owing to population
Neglected tropical diseases (NTDs) are responsible for serious public health problems in much of the world, in developing countries located in Latin America, Africa, and Asia, and can affect non-endemic developed regions, such as North America and Europe, owing to populationMolecules 2020, 25, 2602; doi:10.3390/molecules25112602 www.mdpi.com/journal/moleculesMolecules 2020, 25, 2602 migration and climate change
Compounds based on bisphosphonates belonging to the second and third generation are the main compounds with inhibitory activity on farnesyl pyrophosphate synthase (FPPS), an essential enzyme in the mevalonate pathway, responsible for the production of isoprenoids, such as cholesterol and ergosterol [83]
Summary
Neglected tropical diseases (NTDs) are responsible for serious public health problems in much of the world, in developing countries located in Latin America, Africa, and Asia, and can affect non-endemic developed regions, such as North America and Europe, owing to population. The therapeutic regimens used to control the foremost NTDs have several limitations, especially concerning pharmacological efficacy, toxicity, high costs, and complicated clinical administration As these are diseases mostly related to poverty in developing countries, investment in measures to control these diseases are still insufficient [2,3]. Several strategies have been reported aiming at the development of new drugs with antiparasitic activity, mainly in the context of infections caused by trypanosomatids, such as Leishmania spp [7,8,9,10] and T. cruzi [11,12,13] In this scenario, compounds based on bisphosphonates have been gaining prominence owing to their reported antiparasitic activity [7,8,9,10,11,12,13]. The objective of this work is to present the pharmacological applications of bisphosphonates as potential antiparasitic drugs with an emphasis on the therapeutic control of Chagas disease and leishmaniasis
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