The Potential of Secondary Metabolites from Plants as Drugs or Leads against Trypanosoma cruzi-An Update from 2012 to 2021

Abstract

Background: Chagas disease (American Trypanosomiasis) is classified by the World Health Organization (WHO) as one of the seventeen neglected tropical diseases (NTD), affecting, mainly, several regions of Latin America. Introduction: However, immigration has expanded the range of this disease to other continents. Thousands of patients with Chagas disease die annually, yet no new therapeutics for Chagas disease have been approved, with only nifurtimox and benznidazole available. Treatment with these drugs presents several challenges, including protozoan resistance, toxicity, and low efficacy. Natural products, including the secondary metabolites found in plants, offer a myriad of complex structures that can be sourced directly or optimized for drug discovery. Method: Therefore, this review aims to assess the literature from the last 10 years (2011 – 2021) and present the anti-T. cruzi compounds isolated from plants in this period, as well as briefly discuss computational approaches and challenges in natural product drug discovery. Using this approach, more than 350 different metabolites were divided based on their biosynthetic pathway – alkaloids, terpenoids, flavonoids, polyketides, and phenylpropanoids which displayed activity against different forms of this parasite – epimastigote, trypomastigote and more important, the intracellular form, amastigote. Conclusion: In this aspect, there are several compounds with high potential which could be considered as a scaffold for the development of new drugs for the treatment of Chagas disease – for this, more advanced studies must be performed including pharmacokinetics (PK) and pharmacodynamics (PD) analysis as well as conduction of in vivo assays, these being important limitations in the discovery of new anti-T. cruzi compounds.

Andrographolide: A Diterpenoid from Cymbopogon schoenanthus Identified as a New Hit Compound against Trypanosoma cruzi Using Machine Learning and Experimental Approaches

“…The data set used for training the machine learning models was built in Instant JChem through an extensive literature review on natural products with anti- T. cruzi activity between the years 2012 and 2021 . The data set includes parasite activity against epimastigote, trypomastigote, and/or amastigote forms, parasite strain, cytotoxicity against mammalian cells, and the corresponding cell type.…”

“…The data set used for training the machine learning models was built in Instant JChem through an extensive literature review on natural products with anti-T. cruzi activity between the years 2012 and 2021. 21 The data set includes parasite activity against epimastigote, trypomastigote, and/or amastigote forms, parasite strain, cytotoxicity against mammalian cells, and the corresponding cell type. The data set for virtual screening was a combination of ID and SMILES data, available on the Naturally occurring Plant-Based Anticancer Compound-Activity-Target (NPACT) database, containing 1574 compounds.…”

The Evolution in Pharmacology of Infectious Diseases: 2022

“…Many natural products exhibit significant therapeutic potential and possess a diverse array of biological properties, including antibacterial, antiprotozoal, antimycobacterial, antileishmanial, antitumor, and anti-human immunodeficiency virus (HIV) activities and represent a valuable and fruitful resource for the discovery and development of potent drugs against a variety of diseases (Álvarez-Bardón et al, 2020;Tempone et al, 2021;Lazarin-Bidóia et al, 2022). As such, there are numerous review studies focusing on the potential use of natural products with effects on T. cruzi, providing valuable insights for further investigation (Scotti et al, 2016;Nekoei et al, 2022;Barbosa et al, 2023). For instance, antibiotics such as echinomycin derived from Streptomyces echinatus, exhibit notable anti-T. cruzi activity at nanomolar concentrations (EC 50 of 1.1 nM) (Annang et al, 2015).…”

Trypanocidal and Anti-Inflammatory Effects of Three ent-Kaurane Diterpenoids from Gymnocoronis spilanthoides var. subcordata (Asteraceae)

“…In this sense, the potential of natural products as antiparasitic agents has been demonstrated by the development of ivermectin, artemisinin, quinine and their derivatives, used for the treatment of neglected diseases mainly in developing countries. A vast number of phytochemicals, including terpenoids, alkaloids and phenolic compounds, have been pointed out as promising candidates for the development of drugs against Chagas disease [ 14 , 15 ].…”