Aryl Quinazolinone Derivatives as Novel Therapeutic Agents against Brain-Eating Amoebae

Area of Science:

• Medicinal Chemistry
• Parasitology
• Nanotechnology

Background:

• Naegleria fowleri and Balamuthia mandrillaris are deadly protist pathogens causing severe neurological infections.
• Primary amoebic meningoencephalitis and granulomatous amoebic encephalitis have extremely high mortality rates (>95%).
• Existing treatments for these infections are limited, necessitating novel therapeutic strategies.

Purpose of the Study:

• To synthesize and evaluate novel arylquinazolinone derivatives for antiamoebic activity.
• To assess the efficacy of these compounds against Naegleria fowleri and Balamuthia mandrillaris.
• To investigate the potential of silver nanoparticle conjugation to enhance drug activity.

Main Methods:

• Synthesis of 34 novel arylquinazolinone derivatives.
• Amoebicidal and amoebistatic assays against N. fowleri and B. mandrillaris.
• In vitro cytotoxicity assays against HaCat cells and amoebae-mediated host cell cytopathogenicity assays.
• Conjugation of selected derivatives with silver nanoparticles.

Main Results:

• Several arylquinazolinone derivatives demonstrated significant reduction in B. mandrillaris and N. fowleri viability (P < 0.05).
• The tested compounds effectively reduced parasite-mediated cytopathogenicity against human keratinocytes.
• The synthesized compounds exhibited low cytotoxicity against HaCat cells.
• Conjugation with silver nanoparticles successfully enhanced the antiamoebic activity of the quinazolinone derivatives.

Conclusions:

• Novel arylquinazolinones possess significant antiamoebic properties against brain-eating amoebae.
• These compounds are safe for host cells at effective concentrations.
• Silver nanoparticle conjugation represents a promising strategy to improve the therapeutic efficacy of arylquinazolinones against Naegleria fowleri and Balamuthia mandrillaris.