AI Article Synopsis
- The fungus Rhizopus oryzae ATCC 11145 bioconverts the aromatase inhibitor formestane into two metabolites: a new minor one (3,5α-dihydroxyandrost-2-ene-4,17-dione) and a known major one (4β,5α-dihydroxyandrostane-4,17-dione).
- Structural analysis and bioactivity of these metabolites are documented, underscoring their relevance.
- Molecular modeling reveals that various amino acid residues in the aromatase protein interact with these metabolites, informing potential strategies for developing more effective aromatase inhibitors.
Article Abstract
Bioconversion of the aromatase inhibitor formestane (4-hydroxyandrost-4-ene-3,17-dione) (1) by the fungus Rhizopus oryzae ATCC 11145 resulted in a new minor metabolite 3,5α-dihydroxyandrost-2-ene-4,17-dione (2) and the known 4β,5α-dihydroxyandrostane-4,17-dione (3) as the major product. The structural elucidation and bioactivities of these metabolites are reported herein. Molecular modeling studies of the interactions between these metabolites and the aromatase protein indicated that acidic (D309), basic (R115), polar (T310), aromatic (F134, F221, and W224), and non-polar (I133, I305, A306, V369, V370, L372, V373, M374, and L477) amino acid residues contribute important interactions with the steroidal substrates. These combined experimental and theoretical studies provide fresh insights for the further development of more potent aromatase inhibitors.
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| http://dx.doi.org/10.1016/j.steroids.2016.07.003 | DOI Listing |
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