Unicellular organisms like Naegleria fowleri are generally harmless. However, the organism is known by another – far more ominous name – “brain eating amoeba.” Although N. fowleri typically eat bacteria, but if introduced into humans via nostrils (usually via contaminated water during swimming, ablution, bathing, nasal irrigation etc.) they can use brains as a food source. Though such incidences are fortunately rare, morbidity and mortality rates associated with diseases caused by amoeba are rising, particularly in developing countries, where people rely on water storage systems that can fall foul to contamination. Now, researchers at the American University of Sharjah, United Arab Emirates, have designed novel compounds which, when combined with silver nanoparticles, show promise in killing the amoeba.
N. fowleri is attracted to the chemicals that neurons produce when communicating with one another, and will travel through the nose and olfactory nerve before reaching the brain, where it can cause infections like primary amoebic meningoencephalitis (which causes inflammation and destruction of the brain and its linings) and granulomatous amoebic encephalitis (a rare but usually fatal CNS disease).
“Currently available antimicrobials can cause severe systemic side effects, such as nephrotoxicity, as they are administered intravenously. And that’s one of the reasons why the mortality rate for these diseases is more than 95 percent,” explains Ruqaiyyah Siddiqui at the American University of Sharjah.
Siddiqui and her colleagues tested a variety of quinazolinones and their derivatives in vitro as their antiamoebic effects had not previously been tested. They found that these compounds elicited amoebicidal effects against N. fowleri and Balamuthia mandrillaris, another type of protist pathogen that causes brain infection. The novel compounds alone as well as in combination with silver nanoparticles showed potent effects. They also tested the cytopathogenicity and cytotoxicity of the compounds against amoeba-mediated damage of the human keratinocytes, which resulted in the reduced viability of both pathogens. “We have reported in several studies that the conjugation of silver nanoparticles with novel and existing drugs significantly enhances their effects. Through our experimentation, we have synthesized 34 new quinazolinone derivatives that are effective in killing the amoebae,” Siddiqui and Khan added.
Ruqaiyyah Siddiqui and Naveed Ahmed Khan, another researcher from the American University of Sharjah, now plan to commence further animal and human studies to develop a better understanding of the precise molecular pathways the parasites use to cause disease, with a view to seeking new and effective drug targets.
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References
- R Siddiqui, “Aryl quinazolinone derivatives as novel therapeutic agents against brain-eating amoebae”, ACS Chem. Neurosci, (2020).
