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Updated: Feb 13, 2026

Purification of Extracellular Trypanosomes, Including African, from Blood by Anion-Exchangers Diethylaminoethyl-cellulose Columns
Published on: April 6, 2019
Multi-target mode of action of a Clerodane-type diterpenoid from Polyalthia longifolia targeting African trypanosomes
Godwin U Ebiloma1,2, Evangelos Katsoulis1, John O Igoli3,4
1Institute of Infection, Immunity and Inflammation, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, UK.
Abstract:
Natural products have made remarkable contributions to drug discovery and therapy. In this work we exploited various biochemical approaches to investigate the mode of action of 16-α-hydroxy-cleroda-3,13 (14)-Z-dien-15,16-olide (HDK-20), which we recently isolated from Polyalthia longifolia, on Trypanosoma brucei bloodstream trypomastigotes. HDK20 at concentrations ≥ EC50 (0.4 μg/ml) was trypanocidal, with its effect irreversible after only a brief exposure time (<1 h). Fluorescence microscopic assessment of DNA configuration revealed severe cell cycle defects after 8 h of incubation with the compound, the equivalent of a single generation time. This was accompanied by DNA fragmentation as shown by Terminal deoxynucleotidyl transferase dUTP Nick-End Labelling (TUNEL) assays. HDK-20 also induced a fast and profound depolarisation of the parasites' mitochondrial membrane potential and depleted intracellular ATP levels of T. brucei. Overall, HDK20 showed a multi-target mechanism of action, which provides a biochemical explanation for the promising anti-trypanosomatid activity in our previous report.
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