Anticandidal activity of L-β-(isoxazolin-5-on-2-yl)-alanine due to the inhibition of O-acetyl-L-homoserine sulfhydrylase and cystathionine γ-synthase
- 1Department of Pharmaceutical Technology and Biochemistry, Gdańsk University of Technology, Gdańsk, Poland
- 2Department of Organic Chemistry, Gdańsk University of Technology, Gdańsk, Poland
Abstract
The L-β-(isoxazolin-5-on-2-yl)-alanine (BIA) exhibits in vitro growth inhibitory activity against human pathogenic yeasts of Candida spp, with MIC90 values in 0.5 – 8 µg/mL range. BIA is transported in Candida albicans by the Mup1p permease and then inhibits enzymes of the methionine biosynthetic pathway, O-acetyl-L-homoserine sulfhydrylase Met15p and cystathionine γ-synthase Str2p. The slight, borderline synergistic effect was observed for combination of BIA with L-penicillamine. BIA was found to be a competitive inhibitor of Met15p and Str2p, with Ki values equal to 0.711 mM and 0.912 mM, respectively. Results of the molecular docking analysis of BIA binding at Met15p active centre suggest that this compound could possibly act as a dead-end inhibitor. The same mechanism of Str2p inhibition by BIA is suggested. BIA is the first identified inhibitor of both Met15p and Str2p, exhibiting moderate growth inhibitory activity against human pathogenic yeasts of the Candida genus.
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BibTeX
@article{kuplinska2026anticandidal,
title = {{Anticandidal activity of L-β-(isoxazolin-5-on-2-yl)-alanine due to the inhibition of O-acetyl-L-homoserine sulfhydrylase and cystathionine γ-synthase}},
author = {Aleksandra Kuplińska and Edyta Składanek and Hira Zahoor Rajput and Joanna Stefaniak-Skorupa and Kamila Rząd and Katarzyna Kozłowska-Tylingo and Marek Wojciechowski and Milewska Maria J and Iwona Gabriel and Sławomir Milewski},
journal = {Journal of Enzyme Inhibition and Medicinal Chemistry},
year = {2026},
month = oct,
doi = {10.1080/14756366.2026.2749883},
url = {https://doi.org/10.1080/14756366.2026.2749883},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Anticandidal activity of L-β-(isoxazolin-5-on-2-yl)-alanine due to the inhibition of O-acetyl-L-homoserine sulfhydrylase and cystathionine γ-synthase
AU - Aleksandra Kuplińska
AU - Edyta Składanek
AU - Hira Zahoor Rajput
AU - Joanna Stefaniak-Skorupa
AU - Kamila Rząd
AU - Katarzyna Kozłowska-Tylingo
AU - Marek Wojciechowski
AU - Milewska Maria J
AU - Iwona Gabriel
AU - Sławomir Milewski
PY - 2026
DA - 2026/10/21
JO - Journal of Enzyme Inhibition and Medicinal Chemistry
DO - 10.1080/14756366.2026.2749883
UR - https://doi.org/10.1080/14756366.2026.2749883
AB - The L-β-(isoxazolin-5-on-2-yl)-alanine (BIA) exhibits in vitro growth inhibitory activity against human pathogenic yeasts of Candida spp, with MIC90 values in 0.5 – 8 µg/mL range. BIA is transported in Candida albicans by the Mup1p permease and then inhibits enzymes of the methionine biosynthetic pathway, O-acetyl-L-homoserine sulfhydrylase Met15p and cystathionine γ-synthase Str2p. The slight, borderline synergistic effect was observed for combination of BIA with L-penicillamine. BIA was found to be a competitive inhibitor of Met15p and Str2p, with Ki values equal to 0.711 mM and 0.912 mM, respectively. Results of the molecular docking analysis of BIA binding at Met15p active centre suggest that this compound could possibly act as a dead-end inhibitor. The same mechanism of Str2p inhibition by BIA is suggested. BIA is the first identified inhibitor of both Met15p and Str2p, exhibiting moderate growth inhibitory activity against human pathogenic yeasts of the Candida genus.
SN - 1475-6366
SN - 1475-6374
ER -