Multi-Target-Directed Ligands as Innovative Tools to Combat Trypanosomatid Diseases

Maria      Laura Bolognesi

Abstract

Of the tropical diseases, trypanosomiases and leishmaniases should most concern the pharmaceutical community because of their high prevalence in developing countries and the lack of effective drug treatments. Despite this, they have not historically received much attention in terms of investment and research effort, nor do they now. In very recent years, thanks to the involvement of several nonprofit organizations, the chemotherapeutic options have expanded with the introduction of the first combination therapy. The optimal efficacy and safety of nifurtimox – eflornithine combination against second-stage human African trypanosomiasis is an encouraging first step towards simpler and more affordable therapies. Along the same line, I propose that single chemical entities able to modulate more than one target may prove more efficacious and tolerable than the available arsenal of drugs. Herein, I discuss the pros and cons of this approach, together with examples taken from the recent literature.

Keywords: Neglected tropical diseases, combination therapy, multitarget drug discovery, hybrid compounds, leishmaniasis, trypanosomiasis, multitarget ligands, Nifurtimox benznidazole, toxic organic compound, mucocutaneous disease, chronic human trypanosomiasis, therapeutic compounds, antiretroviral treatment, visceralleishmaniases, axenic amastigote