Temperate Zone Plant Natural Products—A Novel Resource for Activity against Tropical Parasitic Diseases

Abstract

The use of plant-derived natural products for the treatment of tropical parasitic diseases often has ethnopharmacological origins. As such, plants grown in temperate regions remain largely untested for novel anti-parasitic activities. We describe here a screen of the PhytoQuest Phytopure library, a novel source comprising over 600 purified compounds from temperate zone plants, against in vitro culture systems for Plasmodium falciparum, Leishmania mexicana, Trypanosoma evansi and T. brucei. Initial screen revealed 6, 65, 15 and 18 compounds, respectively, that decreased each parasite’s growth by at least 50% at 1–2 µM concentration. These initial hits were validated in concentration-response assays against the parasite and the human HepG2 cell line, identifying hits with EC50 < 1 μM and a selectivity index of >10. Two sesquiterpene glycosides were identified against P. falciparum, four sterols against L. mexicana, and five compounds of various scaffolds against T. brucei and T. evansi. An L. mexicana resistant line was generated for the sterol 700022, which was found to have cross-resistance to the anti-leishmanial drug miltefosine as well as to the other leishmanicidal sterols. This study highlights the potential of a temperate plant secondary metabolites as a novel source of natural products against tropical parasitic diseases.

Drug Discovery for Cutaneous Leishmaniasis: A Review of Developments in the Past 15 Years

“…Known compounds like clinically approved HDAC inhibitors [156] and those found in the Medicines for Malaria Venture pathogen box [157] have shown substantial activity against Leishmania, Plasmodium, and even Schistosoma parasites. In addition, sesquiterpene glycosides [158], flavonoids [159], quinoxaline derivatives [160], and quinazoline derivatives [161] were shown to possess efficacy against Plasmodium and kinetoplastids. Interestingly, researchers have even identified compounds effective against protozoan parasites, including Leishmania, Trypanosoma, Giardia, and Trichomonas [162,163].…”

Chemical Characterization and Leishmanicidal Activity In Vitro and In Silico of Natural Products Obtained from Leaves of Vernonanthura brasiliana (L.) H. Rob (Asteraceae)

“…A wide range of traditional medicine and natural products can be considered for therapy against several diseases, including COVID-19 [ 8 , 9 ], cancer [ 10 , 11 ], parasitic infections [ 12 , 13 ], diabetes [ 14 , 15 ], and obesity [ 16 ]. In fact, the WHO recognizes the importance of traditional medicine, especially in underdeveloped countries, where approximately 85% of the population uses medicinal plants as a therapeutic alternative.…”

Strasseriolides display in vitro and in vivo activity against trypanosomal parasites and cause morphological and size defects in Trypanosoma cruzi

“…More recently, the isolation of compounds from marine organisms and plants has yielded novel trypanocidal and antileishmanial molecules such as quinones, sesquiterpenes lactones, flavonoids, peroxides and various alkaloids with no or low cytotoxicity. Different classes of natural products derived from microbial sources have shown potential as antitrypanosomal and antileishmanial agents [12][13][14][15][16][17][18][19][20][21][22][23][24][25].…”