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Novel Azoles as Antiparasitic Remedies against Brain-Eating Amoebae
Ayaz Anwar1, Mohammad Ridwane Mungroo1, Simal Khan2
1Department of Biological Sciences, School of Science and Technology, Sunway University, Petaling Jaya, Selangor 47500, Malaysia.
Abstract:
Balamuthia mandrillaris and Naegleria fowleri are opportunistic protozoan pathogens capable of producing infection of the central nervous system with more than 95% mortality rate. Previously, we have synthesized several compounds with antiamoebic properties; however, synthesis of compounds that are analogues of clinically used drugs is a highly desirable approach that can lead to effective drug development against these devastating infections. In this regard, compounds belonging to the azole class possess wide range of antimicrobial properties and used clinically. In this study, six novel benzimidazole, indazole, and tetrazole derivatives were synthesized and tested against brain-eating amoebae. These compounds were tested for their amoebicidal and static properties against N. fowleri and B. mandrillaris. Furthermore, the compounds were conjugated with silver nanoparticles and characterized. The synthetic heterocyclic compounds showed up to 72% and 65% amoebicidal activities against N. fowleri and B. mandrillaris respectively, while expressing up to 75% and 70% amoebistatic activities, respectively. Following conjugation with silver nanoparticles, amoebicidal activities of the drugs increased by up to 46 and 36% versus B. mandrillaris and N. fowleri. Minimal effects were observed when the compounds were evaluated against human cells using cytotoxicity assays. In summary, azole compounds exhibited potent activity against N. fowleri and B. mandrillaris. Moreover, conjugation of the azole compounds with silver nanoparticles further augmented the capabilities of the compounds against amoebae.
Insights
Novel azole compounds show potent activity against brain-eating amoebae, *Naegleria fowleri* and *Balamuthia mandrillaris*. Conjugating these compounds with silver nanoparticles further enhanced their amoebicidal and amoebistatic properties.
Area of Science:
- Medicinal Chemistry
- Parasitology
- Nanotechnology
Background:
- *Balamuthia mandrillaris* and *Naegleria fowleri* are protozoan pathogens causing central nervous system infections with high mortality rates (>95%).
- Developing effective treatments against these amoebae is crucial, and exploring clinically relevant drug analogues like azoles is a promising strategy.
Purpose of the Study:
- To synthesize novel benzimidazole, indazole, and tetrazole derivatives based on the azole class.
- To evaluate the synthesized compounds' amoebicidal and amoebistatic activities against *N. fowleri* and *B. mandrillaris*.
- To investigate the effect of conjugating these compounds with silver nanoparticles (AgNPs) on their anti-amoebic efficacy.
Main Methods:
- Synthesis of six novel heterocyclic compounds belonging to the benzimidazole, indazole, and tetrazole families.
- In vitro testing of synthesized compounds for amoebicidal and amoebistatic activity against *N. fowleri* and *B. mandrillaris*.
- Characterization and evaluation of compounds conjugated with silver nanoparticles for enhanced anti-amoebic effects.
- Cytotoxicity assays to assess the safety of compounds against human cells.
Main Results:
- The synthetic heterocyclic compounds demonstrated significant amoebicidal activity (up to 72% against *N. fowleri*, 65% against *B. mandrillaris*) and amoebistatic activity (up to 75% against *N. fowleri*, 70% against *B. mandrillaris*).
- Conjugation with silver nanoparticles markedly increased the amoebicidal activity, with improvements of up to 46% against *B. mandrillaris* and 36% against *N. fowleri*.
- The compounds exhibited minimal cytotoxicity against human cells, indicating a favorable safety profile.
Conclusions:
- Azole-based heterocyclic compounds show potent anti-amoebic activity against *Naegleria fowleri* and *Balamuthia mandrillaris*.
- Conjugation with silver nanoparticles significantly enhances the anti-amoebic efficacy of these azole derivatives.
- These findings suggest that azole-AgNP conjugates represent a promising therapeutic strategy for treating infections caused by these devastating brain-eating amoebae.
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