Evaluating the anti-amoebic activity of putative chemotherapeutic targets and their metal nanoparticle conjugates against Naegleria Fowleri

• Main Author: Kavitha, Rajendran *
• Format: Thesis
• Published: 2020
• Subjects: QR Microbiology; RA Public aspects of medicine; RC Internal medicine
• Online Access: http://eprints.sunway.edu.my/2385/

Naegleria fowleri infects the central nervous system and causes primary amoebic meningoencephalitis (PAM). These brain-eating amoebae invade the nervous system via the nose when contaminated water is deeply inhaled. Subsequently, they invade into the brain tissue; causing severe haemorrhage and inflammation, resulting in widespread brain tissue destruction. Delayed diagnosis with inappropriate treatment available and the devastating nature of the disease results in a mortality rate of 98%. In this study, three groups of compounds were used: antifungals (amphotericin B, nystatin and fluconazole), CNS drugs (phenytoin, phenobarbitone and diazepam) and natural products (cinnamic acid, oleic acid, hesperidin and naringin). The compounds were conjugated with metal nanoparticles and their efficacy against N. fowleri was evaluated. The conjugated compounds were characterized for their physical properties using various techniques. Following that, their anti-amoebic potential against N. fowleri was assessed. The metal nanoparticles-conjugated compounds showed enhanced anti-amoebic activity and reduced host cell cytotoxicity. hesperidin appeared to exhibit the most potent activity as compared to all other compounds. Transcriptomic analysis identified genes that were differentially regulated in cells treated with silver nanoparticles-conjugated hesperidin. These results provide new insights towards the development of therapeutic targets against N. fowleri-associated PAM by repurposing existing drugs and identifying new natural products-based targets.