The parasitic amoebae of concern are named Naegleria fowleri and Balamuthia mandrillaris, and in an infected person they can cause amoebic meningoencephalitis and granulomatous amoebic encephalitis. These organisms are generally found in warm freshwater, such as lakes and rivers, most often in southern states of the U.S.
The amoebae are found in water and soil, and the main route into a body is via the nose or open wounds. The organisms are thermophiles, meaning that as the water temperature rises, their numbers increase. The single-celled microorganisms then gravitate to the central nervous system, where the act upon brain cells.
The symptoms include focal paralysis, seizures, and brainstem symptoms like facial paralysis, difficulty swallowing, and double vision. The condition can be difficult for doctors to diagnose, because it is a rare disease (the main diagnosis is by a biopsy). Most cases are fatal.
Sometimes a cocktail of antimicrobials compounds is successful, but due to the non-targeted nature of these drugs, often the antimicrobials are not effective, lacking specificity. Furthermore, the antimicrobials often carry toxic effects.
To develop a new, more focused antimicrobial, researchers from Sunway University in Malaysia, have been examining quinazolinones. This class of organic chemicals, of growing interest to the field of medicinal chemistry, possess a wide spectrum of biological properties including antibacterial, antifungal, anticonvulsant, anti-inflammatory, anti-HIV, anti-cancerous and analgesic properties.
With the development, the research team synthesized 34 quinazolinone derivatives and proceeded to test these, under laboratory conditions, against N. fowleri and B. mandrillaris.
Some of the compounds, especially those formed of chlorine, methyl or methoxy groups, proved effective and it was later found that the effectiveness could be boosted further when silver nanoparticles were attached to the compounds.
The toxicity for human cells was found to be low. The leading compounds will be taken to the next stage of research, to further assess their amoebae killing properties.
The promising new drug compounds have been described in the journal ACS Chemical Neuroscience. The research paper is titled “Aryl Quinazolinone Derivatives as Novel Therapeutic Agents against Brain-Eating Amoebae.”