Chemotherapy of leishmaniasis: present challenges

Abstract

Cutaneous and visceral leishmaniasis are amongst the most devastating infectious diseases of our time, affecting millions of people worldwide. The treatment of these serious diseases rely on a few chemotherapeutic agents, most of which are of parenteral use and induce severe side-effects. Furthermore, rates of treatment failure are high and have been linked to drug resistance in some areas. Here, we reviewed data on current chemotherapy practice in leishmaniasis. Drug resistance and mechanisms of resistance are described as well as the prospects for applying drug combinations for leishmaniasis chemotherapy. It is clear that efforts for discovering new drugs applicable to leishmaniasis chemotherapy are essential. The main aspects on the various steps of drug discovery in the field are discussed.

Repurposing of Human Kinase Inhibitors in Neglected Protozoan Diseases

“…The liposomal amphotericin B (Figure ) was approved by the FDA for VL having a shorter course and lower toxicity, whereas the oral miltefosine (Figure ) is an effective FDA‐approved treatment against both VL and CL. Some other drugs such as pentamidine and azoles (ketoconazole, itraconazole, and fluconazole) are efficient to treat selected cases of leishmaniasis, but they are not FDA indicated . Two drug candidates, the topical WR‐279,396 (15 % paromomycin + 0.5 % gentamicin) and 18‐methoxycoronaridine (Figure ), are under clinical investigation to evaluate the efficacy and tolerability for CL treatment .…”

Proteomics and Leishmaniasis: Potential Clinical Applications

“…However, the number of treatment options for the disease has not increased accordingly. In fact, there are only a few drugs available, which have side effects and are not always effective . The emergence of resistance in endemic areas is also a matter of concern, as will be discussed later.…”

“…Changes in climate, movement of populations from endemic rural areas to new agricultural or urban zones and the establishment of conflict zones have increased leishmaniasis foci worldwide (revised in ref. [12]). However, the number of treatment options for the disease has not increased accordingly.…”

Effect of isoxazole derivatives of tetrahydrofuran neolignans on intracellular amastigotes of Leishmania (Leishmania) amazonensis: A structure–activity relationship comparative study with triazole‐neolignan‐based compounds

“…Therapeutic care includes administration of drugs, in dividually or in combination. Although used as an alterna tive treatment, these drugs have undesirable toxic effects (Gonzalez et al, 2009;Tiuman, Santos, Ueda-Nakamura, Filho, & Nakamura, 2011;Uliana, Trinconi, & Coelho, 2017). Development of safer and more-effective therapeutic agents is imperative (Lamotte, Späth, Rachidi, & Prina, 2017;Lindoso, Costa, Queiroz, & Goto, 2012;Murray, 2012).…”