Yassmin Isse Wehelie, Naveed Ahmed Khan, Itrat Fatima, Areeba Anwar, Kanwal Kanwal, Khalid M Khan, Ruqaiyyah Siddiqui, Yuh Koon Tong, Ayaz Anwar
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引用次数: 1
Abstract
Background: Acanthamoeba castellanii is a pathogenic free-living amoeba responsible for blinding keratitis and fatal granulomatous amoebic encephalitis. However, treatments are not standardized but can involve the use of amidines, biguanides, and azoles.
Objectives: The aim of this study was to synthesize a variety of synthetic tetrazole derivatives and test their activities against A. castellanii.
Methods: A series of novel tetrazole compounds were synthesized by one-pot method and characterized by NMR and mass spectroscopy. These compounds were subjected to amoebicidal and cytotoxicity assays against A. castellanii belonging to the T4 genotype and human keratinocyte skin cells, respectively. Additionally, reactive oxygen species determination and electron microscopy studies were carried out. Furthermore, two of the seven compounds were conjugated with silver nanoparticles to study their anti-amoebic potential.
Results: A series of seven tetrazole derivatives were synthesized successfully. The selected tetrazoles showed anti-amoebic activities at 10 μM concentration against A. castellanii in vitro. The compounds tested caused increased reactive oxygen species generation in A. castellanii and morphological damage to amoebal membranes. Moreover, conjugation of silver nanoparticles enhanced anti-amoebic effects of two tetrazoles.
Conclusions: The results showed that azole compounds hold promise in the development of new formulations of anti-Acanthamoebic agents.
期刊介绍：
This journal publishes original research articles and state-of-the-art reviews on all aspects of antimicrobial and antitumor chemotherapy. The results of experimental and clinical investigations into the microbiological and pharmacologic properties of antibacterial, antiviral and antitumor compounds are major topics of publication. Papers selected for the journal offer data concerning the efficacy, toxicology, and interactions of new drugs in single or combined applications. Studies designed to determine the pharmacokinetic and pharmacodynamics properties of similar preparations and comparing their efficacy are also included. Special emphasis is given to the development of drug-resistance, an increasing problem worldwide.
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