Activity of octyl gallate against drug-sensitive and buparvaquone-resistant Theileria annulata

Abstract

Theileria annulata, the causative agent of tropical theileriosis, poses a significant threat to cattle industries, a challenge further intensified by increasing drug resistance. In this study, the food-grade phenolic compound octyl gallate (OG) was evaluated for its antitheilerial activity and identified as a potent and selective inhibitor of T. annulata. Comparative screening of gallic acid (GA) derivatives revealed that OG exhibited the strongest activity against T. annulata-transformed cell lines, with IC50 values of 374.0 nM in TaNM cells and 448.7 nM in the buparvaquone-resistant TaXJS cells, while maintaining more than 90% viability in bovine peripheral blood mononuclear cells (PBMCs) at concentrations up to 50 μM, indicating a favorable selectivity profile. At the molecular and cellular levels, OG treatment led to significant downregulation of the parasite genes TaSP and Tap104 and led to the disintegration of the annulate lamellae (AL), a parasite-induced, host-derived structure implicated in host cell manipulation, together with a concentration-dependent induction of apoptosis in TaNM and TaXJS cells. Collectively, these results identify OG as a promising lead compound with activity against T. annulata, combining direct effects on the parasite with apoptosis-associated effects in infected host cells. This study provides experimental support for further investigation of OG as a potential therapeutic option for the control of tropical theileriosis, particularly in the context of emerging drug resistance.