Development of new antileishmanial drugs – current knowledge and future prospects

Abstract

Leishmaniasis is a protozoan vector borne disease prevalent throughout the world and present in at least 88 countries. The parasite is transmitted by infected phlebotomine sandfly bites. While conventional therapies i.e. pentavalent antimonials, amphotericin B and pentamidine continue to play a major role, it is evident that new drugs or strategies must circumvent the limitations, such as a long-term parenteral administration, toxicity, the high cost in endemic countries and the emergence of resistance, that prevail. One of the most promising drugs is miltefosine, a new oral, approved alkylphospholipid for visceral leishmaniasis with only slight adverse effects. Although we have now this recent and encouraging advance, there is still a need to develop safe, efficient and affordable new treatments for the different clinical forms that exist. This review summarises conventional therapy and the current efforts in the discovery of drugs to treat leishmaniasis with the emphasis on drug combinations to enhance efficiency and prevent the emergence of resistance, the investigation of natural products with the objective of offering new bioactive chemical structures and the development of novel antileishmanial targets.

Nanostructured delivery systems with improved leishmanicidal activity: a critical review

“…The need for alternative treatments, in particular to reduce the duration of clinical treatment, led to a program to screen natural products for potential use in leishmaniasis therapy, as recent reviews report, [153][154][155][156] and also to the screening of currently available medicines with potential use in VL. In parallel, quantitative structure-activity relationship (QSAR) study has been used to identify new organic compounds with stronger activity.…”

Therapeutic switching in leishmania chemotherapy: a distinct approach towards unsatisfied treatment needs

“…It is a highly effective and highly costly treatment option for VL which is used as a first-line drug in India, where resistance to pentavalent antimonials is common. The best amphotericin B regimen is 15 doses of 1 mg/kg on alternate days (Pape 2008). Oral amphotericin B is currently being assessed in phase I as well as undergoing (animal) efficacy studies for VL.…”

New Chemotherapeutic Strategies Against Malaria, Leishmaniasis and Trypanosomiases

“…Antimonials must be administered daily for at least three weeks, and the intramuscular injections are often associated with local pain systemic side effects such as nausea, vomiting, weakness and myalgia, abdominal colic, diarrhea, and skin rashes [132]. In addition, their widespread use in areas of high endemicity led to the increasing emergence of resistant strains in Bihar (India), Iran and Peru [133,134].…”