Antifungal Activity, Cytotoxicity and Mechanism of Action of Nitroheteroaryl-1,3,4-thiadiazole Containing N-benzyl and N-methoxyethyl Substitution Against Aspergillus fumigatus
Introduction: This study aimed to evaluate antifungal activity and cytotoxicity of two new nitroheteroaryl-1,3,4-thiadiazole derivatives containing N-methoxyethyl (9) and N-benzyl (10) moiety against Aspergillus fumigatus with a special focus on their mechanism of action at cellular level. Material...
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| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Galenos Publishing House
2021-12-01
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| Series: | Mediterranean Journal of Infection, Microbes and Antimicrobials |
| Subjects: | |
| Online Access: | http://mjima.org/abstract.php?id=258 |
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| Summary: | Introduction: This study aimed to evaluate antifungal activity and cytotoxicity of two new nitroheteroaryl-1,3,4-thiadiazole derivatives containing N-methoxyethyl (9) and N-benzyl (10) moiety against Aspergillus fumigatus with a special focus on their mechanism of action at cellular level.
Materials and Methods: The fungal growth rate was evaluated by microbioassay technique. Ergosterol content of the cell membrane was determined, and morphological changes of fungal compartments were assessed by electron microscopy. Cytotoxicity against Vero and Hep2 cell lines was determined by cell culture technique.
Results: Based on the data obtained, compound 9 showed 31.90-100% inhibition at concentrations of 25-800 μM, while compound 10 presented 24.26-100% inhibition at higher concentrations (25-3200 μM). Compounds 9 and 10 showed minimum fungicidal concentration of 500 and 8000 μM and IC50 values of 43.39 and 1008.67 μM, respectively. Ergosterol content was not meaningfully affected by both compounds. Electron microscopy showed deformation of A. fumigatus hyphae, depletion of hyphae contents, and destruction of cell membrane and membranous organelles in the fungus exposed to both compounds. Compounds 9 and 10 had no obvious cytotoxicity against Vero and Hep2 cell lines in vitro.
Conclusion: Taken together, our results showed that both compounds, especially compound 9, could be considered as potential candidates for developing antifungal drugs against A. fumigatus as the main etiologic agent of life-threatening invasive aspergillosis. |
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| ISSN: | 2147-673X |