Plant-derived compounds against protozoan neglected diseases: toward sustainable drug development

Abstract Neglected tropical diseases (NTDs) are a diverse group of 20 major infectious diseases that prevail in the tropics and subtropics affecting the world’s poorest population living in inadequate housing, sanitation, safe water, and in close contact with infectious vectors and carriers. The NTDs impact 1.4 billion people in the world living in unhygienic and impoverished conditions. The three NTDs with the highest rates of deaths annually are Chagas disease (14,000 cases), sleeping sickness (48,000 cases), and leishmaniasis (51,000 cases); hence, the World Health Organization (WHO) has designated them as the most challenging NTDs. Current therapies for the treatment of these diseases are not very effective with various shortcomings including limited availability, widespread drug resistance, and toxicity. The drugs are also associated with complicated administration procedures that often involve lengthy treatment duration. Moreover, since most infected people are unable to afford them, the mortality rates are high. Therefore the search for efficacious, safe, and affordable drugs for NTDs is of paramount importance. Plants contribute to a vast structural diversity of bioactive compounds that provide unique and myriad opportunities for discovering new drugs. Traditional as well as ethnomedicinal use together with extensive basic laboratory findings have depicted the important role of plants in the prevention and treatment of protozoal diseases for many years. This chapter focuses on such molecules of plant origin; however, the coverage has been restricted to only those molecules which have exhibited substantial potency against the three diseases. The challenges associated with current therapeutic drugs as well as potent plant-derived natural products possessing in vivo and in silico antiparasitic activities, which can further be developed into useful therapeutics to combat these diseases, are described.