Anti-amoebic potential of azole scaffolds and nanoparticles against pathogenic Acanthamoeba
Acanthamoeba spp. are free living amoeba (FLA) which are widely distributed in nature. They are opportunistic parasites and can cause severe infections to the eye, skin and central nervous system. The advances in drug discovery and modifications in the chemotherapeutic agents have shown little imp...
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Elsevier
2020
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| Online Access: | http://eprints.sunway.edu.my/1716/ http://eprints.sunway.edu.my/1716/1/Yow%20Yoon%20Yen%20Anti%20amoebic%20potential.pdf |
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| author | Shweta, W. Anwar, Ayaz * Areeba, A. Sridewi, Nanthini Khalid, Mohammad * Yow, Yoon Yen * Khan, Naveed Ahmed |
| author_facet | Shweta, W. Anwar, Ayaz * Areeba, A. Sridewi, Nanthini Khalid, Mohammad * Yow, Yoon Yen * Khan, Naveed Ahmed |
| author_sort | Shweta, W. |
| building | SU Institutional Repository |
| collection | Online Access |
| description | Acanthamoeba spp. are free living amoeba (FLA) which are widely distributed in nature. They are opportunistic
parasites and can cause severe infections to the eye, skin and central nervous system. The advances in drug
discovery and modifications in the chemotherapeutic agents have shown little improvement in morbidity and
mortality rates associated with Acanthamoeba infections. The mechanism-based process of drug discovery depends
on the molecular drug targets present in the signaling pathways in the genome. Synthetic libraries provide
a platform for broad spectrum of activities due to their desired structural modifications. Azoles, originally a class of synthetic anti-fungal drugs, disrupt the fungal cell membrane by inhibiting the biosynthesis of ergosterol
through the inhibition of cytochrome P450 dependent 14α-lanosterol, a key step of the sterol pathway.
Acanthamoeba and fungi share the presence of similar sterol intermediate, as ergosterol is also the major endproduct
in the sterol biosynthesis in Acanthamoeba. Sterols present in the eukaryotic cell membrane are one of the most essential lipids and exhibit important structural and signaling functions. Therefore, in this review we
highlight the importance of specific targeting of ergosterol present in Acanthamoebic membrane by azole compounds for amoebicidal activity. Previously, azoles have also been repurposed to report antimicrobial, antiparasitic
and antibacterial properties. Moreover, by loading the azoles into nanoparticles through advanced techniques in nanotechnology, such as physical encapsulation, adsorption, or chemical conjugation, the pharmacokinetics and therapeutic index of the drugs can be significantly improved. The current review proposes an important strategy to target Acanthamoeba using synthetic libraries of azoles and their conjugated nanoparticles for the first time. |
| first_indexed | 2025-11-14T21:18:16Z |
| format | Article |
| id | sunway-1716 |
| institution | Sunway University |
| institution_category | Local University |
| language | English |
| last_indexed | 2025-11-14T21:18:16Z |
| publishDate | 2020 |
| publisher | Elsevier |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | sunway-17162021-04-15T05:26:40Z http://eprints.sunway.edu.my/1716/ Anti-amoebic potential of azole scaffolds and nanoparticles against pathogenic Acanthamoeba Shweta, W. Anwar, Ayaz * Areeba, A. Sridewi, Nanthini Khalid, Mohammad * Yow, Yoon Yen * Khan, Naveed Ahmed QH301 Biology Acanthamoeba spp. are free living amoeba (FLA) which are widely distributed in nature. They are opportunistic parasites and can cause severe infections to the eye, skin and central nervous system. The advances in drug discovery and modifications in the chemotherapeutic agents have shown little improvement in morbidity and mortality rates associated with Acanthamoeba infections. The mechanism-based process of drug discovery depends on the molecular drug targets present in the signaling pathways in the genome. Synthetic libraries provide a platform for broad spectrum of activities due to their desired structural modifications. Azoles, originally a class of synthetic anti-fungal drugs, disrupt the fungal cell membrane by inhibiting the biosynthesis of ergosterol through the inhibition of cytochrome P450 dependent 14α-lanosterol, a key step of the sterol pathway. Acanthamoeba and fungi share the presence of similar sterol intermediate, as ergosterol is also the major endproduct in the sterol biosynthesis in Acanthamoeba. Sterols present in the eukaryotic cell membrane are one of the most essential lipids and exhibit important structural and signaling functions. Therefore, in this review we highlight the importance of specific targeting of ergosterol present in Acanthamoebic membrane by azole compounds for amoebicidal activity. Previously, azoles have also been repurposed to report antimicrobial, antiparasitic and antibacterial properties. Moreover, by loading the azoles into nanoparticles through advanced techniques in nanotechnology, such as physical encapsulation, adsorption, or chemical conjugation, the pharmacokinetics and therapeutic index of the drugs can be significantly improved. The current review proposes an important strategy to target Acanthamoeba using synthetic libraries of azoles and their conjugated nanoparticles for the first time. Elsevier 2020-07 Article PeerReviewed text en cc_by_nc_4 http://eprints.sunway.edu.my/1716/1/Yow%20Yoon%20Yen%20Anti%20amoebic%20potential.pdf Shweta, W. and Anwar, Ayaz * and Areeba, A. and Sridewi, Nanthini and Khalid, Mohammad * and Yow, Yoon Yen * and Khan, Naveed Ahmed (2020) Anti-amoebic potential of azole scaffolds and nanoparticles against pathogenic Acanthamoeba. Acta Tropica, 211. p. 105618. ISSN 0001-706X http://doi.org/10.1016/j.actatropica.2020.105618 doi:10.1016/j.actatropica.2020.105618 |
| spellingShingle | QH301 Biology Shweta, W. Anwar, Ayaz * Areeba, A. Sridewi, Nanthini Khalid, Mohammad * Yow, Yoon Yen * Khan, Naveed Ahmed Anti-amoebic potential of azole scaffolds and nanoparticles against pathogenic Acanthamoeba |
| title | Anti-amoebic potential of azole scaffolds and nanoparticles against pathogenic Acanthamoeba |
| title_full | Anti-amoebic potential of azole scaffolds and nanoparticles against pathogenic Acanthamoeba |
| title_fullStr | Anti-amoebic potential of azole scaffolds and nanoparticles against pathogenic Acanthamoeba |
| title_full_unstemmed | Anti-amoebic potential of azole scaffolds and nanoparticles against pathogenic Acanthamoeba |
| title_short | Anti-amoebic potential of azole scaffolds and nanoparticles against pathogenic Acanthamoeba |
| title_sort | anti-amoebic potential of azole scaffolds and nanoparticles against pathogenic acanthamoeba |
| topic | QH301 Biology |
| url | http://eprints.sunway.edu.my/1716/ http://eprints.sunway.edu.my/1716/ http://eprints.sunway.edu.my/1716/ http://eprints.sunway.edu.my/1716/1/Yow%20Yoon%20Yen%20Anti%20amoebic%20potential.pdf |