Anti-amoebic potential of azole scaffolds and nanoparticles against pathogenic Acanthamoeba

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

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Official URL: http://doi.org/10.1016/j.actatropica.2020.105618

Abstract

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.

Item Type: Article
Uncontrolled Keywords: Azole; Free-living amoeba; Acanthamoeba; Anti-amoebic; Ergosterol pathway
Subjects: Q Science > QH Natural history > QH301 Biology
Divisions: Others > Non Sunway Academics
Sunway University > School of Engineering and Technology [formerly School of Science and Technology until 2020] > Sunway Centre for Electrochemical Energy and Sustainable Technology [formerly Graphene and Advanced 2D Materials Research Group until June 2023]
Sunway University > School of Medical and Life Sciences [formerly School of Healthcare and Medical Sciences until 2020] > Dept. Biological Sciences
Depositing User: Dr Janaki Sinnasamy
Related URLs:
Date Deposited: 15 Apr 2021 05:26
Last Modified: 15 Apr 2021 05:26
URI: http://eprints.sunway.edu.my/id/eprint/1716

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