The Potential of Secondary Metabolites from Plants as Drugs or Leads Against Protozoan Neglected Diseases - Part I

Abstract

Infections with protozoan parasites are a major cause of disease and mortality in many tropical countries of the world. Diseases caused by species of the genera Trypanosoma (Human African Trypanosomiasis and Chagas Disease) and Leishmania (various forms of Leishmaniasis) are among the seventeen "Neglected Tropical Diseases" (NTDs) defined as such by WHO due to the neglect of financial investment into research and development of new drugs by a large part of pharmaceutical industry and neglect of public awareness in high income countries. Another major tropical protozoan disease is malaria (caused by various Plasmodium species), which -although not mentioned currently by the WHO as a neglected disease- still represents a major problem, especially to people living under poor circumstances in tropical countries. Malaria causes by far the highest number of deaths of all protozoan infections and is often (as in this review) included in the NTDs. The mentioned diseases threaten many millions of lives world-wide and they are mostly associated with poor socioeconomic and hygienic environment. Existing therapies suffer from various shortcomings, namely, a high degree of toxicity and unwanted effects, lack of availability and/or problematic application under the life conditions of affected populations. Development of new, safe and affordable drugs is therefore an urgent need. Nature has provided an innumerable number of drugs for the treatment of many serious diseases. Among the natural sources for new bioactive chemicals, plants are still predominant. Their secondary metabolism yields an immeasurable wealth of chemical structures which has been and will continue to be a source of new drugs, directly in their native form and after optimization by synthetic medicinal chemistry. The current review, published in two parts, attempts to give an overview on the potential of such plant-derived natural products as antiprotozoal leads and/or drugs in the fight against NTDs.

Secondary metabolites in floral nectar reduce parasite infections in bumblebees

“…We infected bees with Crithidia, then fed them sugar solutions containing either one of eight naturally occurring nectar chemicals (table 1) or a control (electronic supplementary material, figure S1). Given their medicinal and anti-trypanosome effects in other contexts [4,5], we predicted that secondary metabolites would lower bee parasite infection. Second, for the alkaloid anabasine, which most strongly reduced Crithidia counts in bees, we used replicate microcolonies to test the individual and combined effects of parasite infection and diet chemistry on bee survival and reproduction (electronic supplementary material, figure S1).…”

Activities of Psilostachyin A and Cynaropicrin against Trypanosoma cruzi In Vitro and In Vivo

“…In fact, despite them comprising Ͻ1 percent of known chemical compounds (DNP 2013 [http://dnp.chemnetbase.com/tour/]; Reaxys 2013 [https://www.reaxys.com/documentation/about _query.htm]), they have supplied or inspired more than half of all new drugs introduced to the market in the last 3 decades (6). The largest known group of natural products are the sesquiterpenes, of which about 10,000 have been described (7,8). About 6,000 of them are sesquiterpene lactones (STLs), meaning that they possess at least one lactone group (7).…”

Phenolic Constituents of Medicinal Plants with Activity against Trypanosoma brucei

“…Moreover, the increase of drug resistant forms emphasize the urgent need for new drugs against HAT. The potential of natural products as lead compounds in drug development is well known and many natural products have shown activity against T. brucei and other parasites causing NTDs [13,14]. In the present communication we report on the results obtained by screening a library of 440 chemically diverse natural products obtained from medicinal plants against T. brucei leading to the discovery of a variety of compounds with significant anti-trypanosomal activity in vitro.…”