Abstract
A novel series of conjugates of the antifungal antibiotic amphotericin B (AmB) with benzoxaboroles was synthesized. Antifungal activity of new compounds was tested on yeastβ Candida albicans and Cryptococcus humicolus and filamentous fungi Aspergillus niger and Fusarium oxysporum using the broth microdilution method. The potency of di-modified derivatives against the tested strains was similar to that of the parent AmB. New derivatives demonstrated differential toxicity against human cells (colon epithelium or red blood cells). The di-modified conjugate 2-(N,N-dimethylamino)ethylamide of 3′-N-[3-(1-hydroxy-1,3-dihydrobenzo[c][1,2]oxaborol-7-yl)propanoyl] AmB (9) showed the best combination of a high antifungal activity with a low cytotoxic and hemolytic potency.
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Acknowledgements
We are grateful to Natalia M Malyutina (Gause Institute of New Antibiotics, Moscow) for HPLC analyses. This study was supported by the Russian Foundation for Basic Research grants 13-03-00643-a and 16-34-60110. NMR studies were partly supported by the Russian Science Foundation grant 14-14-00598.
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Tevyashova, A., Korolev, A., Trenin, A. et al. New conjugates of polyene macrolide amphotericin B with benzoxaboroles: synthesis and properties. J Antibiot 69, 549–560 (2016). https://doi.org/10.1038/ja.2016.34
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DOI: https://doi.org/10.1038/ja.2016.34
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