REPURPOSING CNS DRUGS ZONISAMIDE AND PERAMPANEL AS A POTENTIAL THERAPEUTIC AGAINST ACANTHAMOEBA-INDUCED GAE

Abstract

A  free-living, soil- and water-borne, biphasic, opportunistic FLA, Acanthamoeba castellanii, causes severe CNS infections especially in human being, such as GAE and pariculry eye infection like AK. Treatment challenges stem from the absence of safe and effective drugs, barrier-impaired entry into the central nervous system (i.e., the BBB), as well as the amoeba's cyst-forming ability. Most of the drug is currently under development, and there is limited information regarding appropriate dose or concentrations, administration schedule, timing parameters, therapeutic purpose as well as delivery pathway. Therefore, repurposing drugs is an ideal strategy for promptly addressing A. castellanii infection. This reseach sought to determine the effectiveness of two approved anti-epileptic drugs, Zonisamide (A) and perampanel (B) against T4-genotype A. castellanii in combating amoebic pathogens. Both drugs (A and B) exhibited potent antiamoebic activity with IC₅₀/24 hr values of 58.02 ± 1.22 and 57.155 ± 0.00 µg/mL. Tthey reduced cyst viability by 70% and 62%, respectively. Zonisamide inhibited phenotypic transformation significantly at 50 µM, whereas perampanel required higher concentrations. Both drugs effectively reduced host cell cytopathogenicity and demonstrated moderate toxicity towards HaCaT cells at lower concentrations. Amoebic morphological changes induced by drug treatment were observed using light microscopy during the assessment. These results showed that both drugs exhibit promising potential as repurposed drugs against AGE caused by A. castellanii, representing a significant advancement in drug development targeting all stages of the pathogen.