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Background <p><i>Rhizopus </i>spp. is a major cause of mucormycosis, a severe infectious disease with high morbidity and mortality. Treatment is challenging due to rising antifungal resistance. Glycosylation is a crucial technique for enhancing the properties of phenolic compounds like eugenol. The present study aims to examine the antifungal efficacy of eugenol glycoconjugates against azole and amphotericin B-resistant <i>Rhizopus</i> isolates.</p> Methods and results <p> Out of 50 soil samples, 12 isolates belonging to Mucorales were obtained, of which 7 were identified as <i>Rhizopus </i>spp. via&#xa0;&#xa0;18S ITS sequencing. Antifungal susceptibility testing (AST) revealed that all <i>Rhizopus</i> isolates were resistant to amphotericin B (MIC &gt; 1&#xa0;µg/mL). Most isolates also showed resistance towards posaconazole (MIC &gt; 1&#xa0;µg/mL) and itraconazole (MIC &gt; 2&#xa0;µg/mL). AST of eugenol glycoconjugate (coded 6g) showed efficacy against resistant <i>Rhizopus</i> isolates, with MIC values ranging from 6.25&#xa0;µg/mL to 25&#xa0;µg/mL. Flow cytometry confirmed its fungicidal activity, correlating with MIC data. Compound 6g significantly reduced conidial germination within 24&#xa0;h and exhibited no cytotoxicity on A549 lung cancer cells. In-silico analysis revealed a negative binding affinity of compound 6g for the spore coat protein CotH3, which could be a potential antifungal target.</p> Conclusion <p>Compound 6g could be an potential antifungal molecule against resistant <i>Rhizopus</i> spp, which requires further studies.</p>

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A comprehensive in vitro and in silico assessment of eugenol glycoconjugates against azole and amphotericin B resistant Rhizopus spp.

  • 期刊论文

  • 发表日期：

    2025年6月12日

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  • Pooja Sen,
  • Lovely Gupta,
  • Aastha Chauhan,
  • Lakshmi Goswami,
  • Asish K. Bhattacharya,
  • Abhishek Sengupta,
  • Pooja Vijayaraghavan

摘要

Background

Rhizopus spp. is a major cause of mucormycosis, a severe infectious disease with high morbidity and mortality. Treatment is challenging due to rising antifungal resistance. Glycosylation is a crucial technique for enhancing the properties of phenolic compounds like eugenol. The present study aims to examine the antifungal efficacy of eugenol glycoconjugates against azole and amphotericin B-resistant Rhizopus isolates.

Methods and results

Out of 50 soil samples, 12 isolates belonging to Mucorales were obtained, of which 7 were identified as Rhizopus spp. via  18S ITS sequencing. Antifungal susceptibility testing (AST) revealed that all Rhizopus isolates were resistant to amphotericin B (MIC > 1 µg/mL). Most isolates also showed resistance towards posaconazole (MIC > 1 µg/mL) and itraconazole (MIC > 2 µg/mL). AST of eugenol glycoconjugate (coded 6g) showed efficacy against resistant Rhizopus isolates, with MIC values ranging from 6.25 µg/mL to 25 µg/mL. Flow cytometry confirmed its fungicidal activity, correlating with MIC data. Compound 6g significantly reduced conidial germination within 24 h and exhibited no cytotoxicity on A549 lung cancer cells. In-silico analysis revealed a negative binding affinity of compound 6g for the spore coat protein CotH3, which could be a potential antifungal target.

Conclusion

Compound 6g could be an potential antifungal molecule against resistant Rhizopus spp, which requires further studies.