Alkyl gallates disrupt Trypanosoma brucei lipid droplets

African trypanosomiasis is a deadly disease that affects humans and animals, with treatment hindered by drug toxicity and resistance, highlighting the need for alternative therapies. Alkyl gallates, which are plant-derived phenolipids used in the food, cosmetics, and pharmaceutical industries, have been shown to have potent anti-microbial activity; however, their mechanism of action is still unclear. This study investigated the effects of selected alkyl gallates on Trypanosoma brucei. The in vitro anti-trypanosomal and cytotoxicity of the alkyl gallates were determined using the alamarBlue assay. The effects of the alkyl gallates on lipid droplet dynamics were studied using BODIPY493/503 dye and an endogenously tagged lipid droplet kinase cell line which served as a protein marker of lipid droplets. In vitro treatment with octyl and lauryl gallates resulted in rapid cell death with low IC₅₀ of 0.7 µM and 0.04 µM respectively. Octyl gallate treatment significantly reduced lipid droplet number within 30 minutes and by 2 hours most cells lacked lipid droplets; however, lipid droplets rebounded once the drug pressure was removed. These results show that alkyl gallates rapidly disrupt lipid droplet homeostasis in Trypanosoma brucei. Thus, these gallates could serve as a useful cell biology tool to dissect lipid droplet biogenesis and function in trypanosomes.