Sustainable Drugs against NTDs: Lessons learned from investigating the potential use of propolis-based natural products for treating various forms of human and animal trypanosomiasis

Diseases caused by kinetoplastid parasites such as various species of Trypanosomes and Leishmania represent some of the Neglected Tropical Diseases (NTDs). However, millions of people, and their domesticated animals, living in endemic regions across the globe are at risk of these NTDs. All of the associated human and veterinary conditions can be disabling or fatal if not adequately treated, and no vaccines are available. Still, drug treatment is hampered by the challenges of drug resistance and toxicity to the mostly very old drugs. We have been researching the potential use of propolis-based natural products as a sustainable treatment option. Propolis is a resinous substance that bees harvest from nearby vegetation to protect themselves naturally from microbial infection. Our interdisciplinary team have collected propolis from various geographical locations across the globe and has tested the crude and purified extracts on various strains of these parasites. Unique new compounds with potent antiparasitic activity, particularly have been identified. Our results show that propolis and some of the phytochemicals isolated from it, have no in vitro growth inhibition against mammalian cells, but displayed low EC50 against Trypanosoma and Leishmania species, without a loss of activity against diamidine- and arsenical-resistant or phenanthridine-resistant T. brucei strains, or a miltefosine-resistant L. mexicana strain. These results provide sufficient scope for further investigations of propolis-derived natural compounds for the rational development of sustainable drugs against human or veterinary diseases caused by these parasites.