Screening Marine Natural Products for New Drug Leads against Trypanosomatids and Malaria

Abstract

Neglected Tropical Diseases (NTD) represent a serious threat to humans, especially for those living in poor or developing countries. Almost one-sixth of the world population is at risk of suffering from these diseases and many thousands die because of NTDs, to which we should add the sanitary, labor and social issues that hinder the economic development of these countries. Protozoan-borne diseases are responsible for more than one million deaths every year. Visceral leishmaniasis, Chagas disease or sleeping sickness are among the most lethal NTDs. Despite not being considered an NTD by the World Health Organization (WHO), malaria must be added to this sinister group. Malaria, caused by the apicomplexan parasite Plasmodium falciparum, is responsible for thousands of deaths each year. The treatment of this disease has been losing effectiveness year after year. Many of the medicines currently in use are obsolete due to their gradual loss of efficacy, their intrinsic toxicity and the emergence of drug resistance or a lack of adherence to treatment. Therefore, there is an urgent and global need for new drugs. Despite this, the scant interest shown by most of the stakeholders involved in the pharmaceutical industry makes our present therapeutic arsenal scarce, and until recently, the search for new drugs has not been seriously addressed. The sources of new drugs for these and other pathologies include natural products, synthetic molecules or repurposing drugs. The most frequent sources of natural products are microorganisms, e.g., bacteria, fungi, yeasts, algae and plants, which are able to synthesize many drugs that are currently in use (e.g. antimicrobials, antitumor, immunosuppressants, etc.). The marine environment is another well-established source of bioactive natural products, with recent applications against parasites, bacteria and other pathogens which affect humans and animals. Drug discovery techniques have rapidly advanced since the beginning of the millennium. The combination of novel techniques that include the genetic modification of pathogens, bioimaging and robotics has given rise to the standardization of High-Performance Screening platforms in the discovery of drugs. These advancements have accelerated the discovery of new chemical entities with antiparasitic effects. This review presents critical updates regarding the use of High-Throughput Screening (HTS) in the discovery of drugs for NTDs transmitted by protozoa, including malaria, and its application in the discovery of new drugs of marine origin.

Colombian Contributions Fighting Leishmaniasis: A Systematic Review on Antileishmanials Combined with Chemoinformatics Analysis

“…In addition, other sources should also be examined to look for novel, effective leishmanicidal agents. For instance, marine organisms have been considered as promising suppliers of compounds with novel structures and noteworthy antiparasitic activity [40][41][42], including antileishmanial properties [43][44][45]. In this sense, it may be worthwhile considering marine specimens in future studies, especially marine microorganisms, whose chemical composition and biological activity-to our knowledge-remain to be deeply explored.…”

Potentials of marine natural products against malaria, leishmaniasis, and trypanosomiasis parasites: a review of recent articles

“…Malaria, leishmaniasis, and trypanosomiasis are caused by parasitic protozoa of the genus Plasmodium species, Leishmania (over 20 Leishmania species), and Trypanosoma [ Trypanosoma brucei complex—human African trypanosomiasis (sleeping sickness) and Trypanosoma cruzi —American trypanosomiasis (Chagas disease)], respectively [ 1 , 4 , 5 ]. According to the World Health Organization (WHO) world malaria report 2019, an estimated 228 million cases of malaria and 405 000 deaths occurred worldwide in 2018, and six sub-Saharan African countries are the most affected [ 1 ].…”

“…These limitations range from poor absorption, resistance, lack of efficacy, toxicity and long duration of treatment. These have been discussed in details in other published review articles [ 7 , 8 ].…”

“…Moreover, due to the frightening resistance of the parasites to the available drugs, the search and development of novel alternative therapeutics are imperatively necessary. Fortunately, natural products are not only very useful and active on their own but also are used as templates for the synthesis and development of other compounds [ 8 ]. Marine natural products (MNPs) are bioactive metabolites sourced from marine organisms including microbes, invertebrates and plants.…”

“…Marine natural products (MNPs) are bioactive metabolites sourced from marine organisms including microbes, invertebrates and plants. MNPs from marine habitats composed of an enormous repository of diverse chemical structures and will continue to be a source of novel therapeutics, either directly in their original form or after optimization through synthetic medicinal chemistry [ 8 , 9 ]. In the past few years, there has been a renaissance in natural product discovery from the marine environment.…”