A comprehensive review of patented antileishmanial agents

Abstract

On 14 October 2010, the WHO reported that more than 1 billion people worldwide who live in remote rural areas are affected by neglected tropical diseases. Leishmaniasis is caused by protozoa of more than 20 different species in humans. The three major forms of disease are cutaneous, mucocutaneous and visceral leishmaniasis (VL). Cutaneous leishmaniasis causes an ulcer on exposed parts of the body and it was estimated that 0.7–1.3 million cases occur worldwide annually. Mucocutaneous leishmaniasis leads to destruction of mucous membranes in various parts of the body and it was reported that it occurs widely in South America. VL is a deadly disease and it is characterized by various symptoms, such as anemia, fever, fatigue and weight loss. The WHO estimated that 200,000–400,000 cases per annum of VL occur worldwide. Although different drugs and drug combinations are used for leishmaniasis, US FDA-approved drugs are limited. Miltefosine is the only drug approved for all forms of leishmaniasis and AmBisome® is approved for VL. Moreover, the drugs used for leishmaniasis have severe side effects. The article summarizes the patents filed between January 2010 and June 2013 for antileishmanial activity. The article covers only the chemical agents and excludes the vaccines and the peptides. A large number of compounds are filed for antileishmanial activity annually, but only a few are more potent than reference drugs such as miltefosine, pentamidine and metronidazole. In addition, most of the compounds are not as efficient as amphotericin B. Therefore, there is a need for novel compounds that are not only potent than the FDA-approved AmBisome and miltefosine, but are also less toxic and more cost effective in humans. This article provides an eclectic compilation of different classes of compounds that are active against amastigotes (the protozoa form found in humans) for the treatment of leishmaniasis.