Cellular apoptosis and cell cycle arrest as potential therapeutic targets for eugenol derivatives in Candida auris
Candida auris, the youngest Candida species, is known to cause candidiasis and candidemia in humans and has been related to several hospital outbreaks. Moreover, Candida auris infections are largely resistant to the antifungal drugs currently in clinical use, necessitating the development of novel m...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2023-01-01
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| Series: | PLoS ONE |
| Online Access: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10284410/?tool=EBI |
| _version_ | 1797795982150205440 |
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| author | Hammad Alam Vartika Srivastava Windy Sekgele Mohmmad Younus Wani Abdullah Saad Al-Bogami Julitha Molepo Aijaz Ahmad |
| author_facet | Hammad Alam Vartika Srivastava Windy Sekgele Mohmmad Younus Wani Abdullah Saad Al-Bogami Julitha Molepo Aijaz Ahmad |
| author_sort | Hammad Alam |
| collection | DOAJ |
| description | Candida auris, the youngest Candida species, is known to cause candidiasis and candidemia in humans and has been related to several hospital outbreaks. Moreover, Candida auris infections are largely resistant to the antifungal drugs currently in clinical use, necessitating the development of novel medications and approaches to treat such infections. Following up on our previous studies that demonstrated eugenol tosylate congeners (ETCs) to have antifungal activity, several ETCs (C1-C6) were synthesized to find a lead molecule with the requisite antifungal activity against C. auris. Preliminary tests, including broth microdilution and the MUSE cell viability assay, identified C5 as the most active derivative, with a MIC value of 0.98 g/mL against all strains tested. Cell count and viability assays further validated the fungicidal activity of C5. Apoptotic indicators, such as phosphatidylserine externalization, DNA fragmentation, mitochondrial depolarization, decreased cytochrome c and oxidase activity and cell death confirmed that C5 caused apoptosis in C. auris isolates. The low cytotoxicity of C5 further confirmed the safety of using this derivative in future studies. To support the conclusions drawn in this investigation, additional in vivo experiments demonstrating the antifungal activity of this lead compound in animal models will be needed. |
| first_indexed | 2024-03-13T03:26:16Z |
| format | Article |
| id | doaj.art-67eebb6a90624e00b8463371fbc18bf5 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-03-13T03:26:16Z |
| publishDate | 2023-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-67eebb6a90624e00b8463371fbc18bf52023-06-25T05:31:11ZengPublic Library of Science (PLoS)PLoS ONE1932-62032023-01-01186Cellular apoptosis and cell cycle arrest as potential therapeutic targets for eugenol derivatives in Candida aurisHammad AlamVartika SrivastavaWindy SekgeleMohmmad Younus WaniAbdullah Saad Al-BogamiJulitha MolepoAijaz AhmadCandida auris, the youngest Candida species, is known to cause candidiasis and candidemia in humans and has been related to several hospital outbreaks. Moreover, Candida auris infections are largely resistant to the antifungal drugs currently in clinical use, necessitating the development of novel medications and approaches to treat such infections. Following up on our previous studies that demonstrated eugenol tosylate congeners (ETCs) to have antifungal activity, several ETCs (C1-C6) were synthesized to find a lead molecule with the requisite antifungal activity against C. auris. Preliminary tests, including broth microdilution and the MUSE cell viability assay, identified C5 as the most active derivative, with a MIC value of 0.98 g/mL against all strains tested. Cell count and viability assays further validated the fungicidal activity of C5. Apoptotic indicators, such as phosphatidylserine externalization, DNA fragmentation, mitochondrial depolarization, decreased cytochrome c and oxidase activity and cell death confirmed that C5 caused apoptosis in C. auris isolates. The low cytotoxicity of C5 further confirmed the safety of using this derivative in future studies. To support the conclusions drawn in this investigation, additional in vivo experiments demonstrating the antifungal activity of this lead compound in animal models will be needed.https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10284410/?tool=EBI |
| spellingShingle | Hammad Alam Vartika Srivastava Windy Sekgele Mohmmad Younus Wani Abdullah Saad Al-Bogami Julitha Molepo Aijaz Ahmad Cellular apoptosis and cell cycle arrest as potential therapeutic targets for eugenol derivatives in Candida auris PLoS ONE |
| title | Cellular apoptosis and cell cycle arrest as potential therapeutic targets for eugenol derivatives in Candida auris |
| title_full | Cellular apoptosis and cell cycle arrest as potential therapeutic targets for eugenol derivatives in Candida auris |
| title_fullStr | Cellular apoptosis and cell cycle arrest as potential therapeutic targets for eugenol derivatives in Candida auris |
| title_full_unstemmed | Cellular apoptosis and cell cycle arrest as potential therapeutic targets for eugenol derivatives in Candida auris |
| title_short | Cellular apoptosis and cell cycle arrest as potential therapeutic targets for eugenol derivatives in Candida auris |
| title_sort | cellular apoptosis and cell cycle arrest as potential therapeutic targets for eugenol derivatives in candida auris |
| url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10284410/?tool=EBI |
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