LAUSR

Brain-eating amoebae cause devastating infections of central nervous system in humans, having a mortality rate of 95%. There are limited effective therapeutic options available clinically for treating granulomatous amoebic encephalitis and primary amoebic meningoencephalitis caused by Acanthamoeba castellanii and Naegleria fowleri, respectively. Here we report for the first time that guanabenz conjugated to gold and silver nanoparticles has significant antiamoebic activity against both A. castellanii and N. fowleri. Gold and silver conjugated guanabenz nanoparticles were synthesized by one-phase reduction method and were characterized by ultraviolet-visible spectrophotometry and atomic force microscopy. Both metals were facilely stabilized by the coating of guanabenz which was examined by surface plasmon resonance determination. The average size of gold nanoconjugated guanabenz was found to be 60 nm, whereas, silver nanoparticles were produced in larger size distribution with the average diameter of around 100 nm. Guanabenz and its noble metal nanoconjugates exhibited potent antiamoebic effects in the range of 2.5 to 100 µM against both amoebae. Nanoparticles conjugation enhanced the antiamoebic effects of guanabenz, as more potent activity was observed at lower effective concentration (2.5 and 5 µM) compared to drug alone. Moreover, encystation and excystation assays revealed that guanabenz inhibits the interconversion between the trophozoite and cyst forms of A. castellanii. Cysticdal effects against N. fowleri were also observed. Notably, pre-treatment of A. castellanii with guanabenz and its nanoconjugates exhibited significant reduction in the host cell cytopathogenicity from 65% to 38% and 2% in case of gold and silver nanoconjugates, respectively. Moreover, the cytotoxic evaluation of guanabenz and nanoconjugates revealed negligible cytotoxicity against human cells. Guanabenz is already approved for hypertension and crosses the blood-brain barrier; the results of our current study suggest that guanabenz and its conjugated gold and silver nanoparticles can be repurposed as a potential drug for treating brain eating amoebic infections.