The Kinetoplastid Chemotherapy Revisited: Current Drugs, Recent Advances and Future Perspectives

Abstract

Leishmaniasis, African sleeping sickness and Chagas disease, caused by the kinetoplastid parasites Leishmania spp, Trypanosoma brucei and Trypanosoma cruzi, respectively, are among the most important parasitic diseases, affecting millions of people and considered to be within the most relevant group of neglected tropical diseases. The main alternative to control such parasitosis is chemotherapy. Nevertheless, the current chemotherapeutic treatments are far from being satisfactory. This review outlines the current understanding of different drugs against leishmaniasis, African sleeping sickness and Chagas disease, their mechanism of action and resistance. Recent approaches in the area of anti-leishmanial and trypanocidal therapies are also enumerated, new modulators from the mode of action, development of new formulations of old drugs, therapeutic switching and "in silico" drug design.

Ddi1-like protein from Leishmania major is an active aspartyl proteinase

“…These observations together suggest that new and novel antiparasitic drugs are required. Therefore, the development of alternative drugs for the treatment of the different clinical forms of leishmaniasis is a priority for controlling the disease (Croft et al 2006;Castillo et al 2010). Great efforts have been made to identify potential chemotherapeutic targets in the genome and proteome of Leishmania sp., in the hope of devising more effective treatments (Myler 2008;Concu et al 2009;Chawla and Madhubala 2010).…”

Immunocytochemistry of Proteases in the Study of Leishmania Physiology and Host-Parasite Interaction

“…Since the 1940s, the pentavalent antimony compounds (e.g., Glucantime, Pentostam, or branded pentavalent formulations) have been the mainstays of antileishmanial therapy (Aït-Oudhia et al, 2011). Although these drugs are usually effective, they produce serious side effects, present difficulties of administration and high cost, the parasite persists in the scars of clinically cured patients (Schubach et al, 1998), and drug resistance has been observed (Castillo et al, 2010). Second-line drugs are used in areas with high rates of unresponsiveness to antimonial treatment or when it was not possible to administrate it.…”

Multiple effects of pepstatin A on Trypanosoma cruzi epimastigote forms

“…An estimated 8-10 million people are living with T. cruzi infection in the Latin America (Rassi et al 2010). Compounding this scenario, the available chemotherapy for Chagas' disease is unsatisfactory (Castillo et al 2010). Therefore, novel anti-T. cruzi drugs, ideally directed against new parasite targets, are urgently needed (Sánchez-Sancho et al 2010).…”