Chapter 8 - Phytochemicals With Antileishmanial Activity: Prospective Drug Targets

Abstract

Abstract Protozoan parasites are among the most common causative agents of some of the major tropical diseases occurring in both humans and domestic animals, leading to enormous loss of life and productivity. Leishmaniases are classified as “neglected tropical diseases” with a huge global burden of vector-borne diseases caused by parasites belonging to the genus Leishmania . Typically manifested in visceral, cutaneous, and mucocutaneous forms, leishmaniasis is endemic in some regions of Asia, Africa, and South America. Visceral leishmaniasis (VL) is the most severe clinical appearance of this ailment, known as kala-azar in the Indian subcontinent. Characterized by its effect on the internal organs—particularly the liver, spleen, and bone marrow—VL is often associated with marked suppression of the host's cell-mediated immune response, leading to severe morbidity, even mortality, if left untreated. The management of leishmaniasis depends solely on a limited range of drugs, since a vaccine to combat the disease is not available till date. Pentavalent antimonials are the oldest and foremost line of therapeutics, despite shortcomings like prolonged intravenous regimen, lack of efficacy, and side effects. The other alternatives like pentamidine and amphotericin B also suffer from the limitation of toxicity, while the liposomal formulation of the latter is too expensive. The situation is further aggravated due to the growing unresponsiveness of VL to the antimonials. Even miltefosine, the only oral formulation of an anticancer agent introduced for the treatment of kala-azar in India, has also indicated potential resistance, including concerns about the eventuality of teratogenicity. Thus, it is an ongoing challenge to discover new drugs for the treatment of leishmaniasis. Identification of a molecular target is an important step in drug development against any particular disease. It is expected that the plant kingdom would provide valuable “leads” that could be explored in order to design novel therapeutic agents specifically active against leishmania parasites. A glimpse of the recent findings on prospective compounds, their mechanism of action, and development of potent analogues based on the natural templates will be presented in this chapter.