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Synthesis and bioconversions of formestane
Glenroy D A Martin1, Javier Narvaez, Anne Marti
1Chemistry, Biochemistry and Physics Department, The University of Tampa , 401 West Kennedy Boulevard, Tampa, Florida 33606-1490, United States.
Journal of Natural Products
|October 1, 2013
Summary
New steroidal aromatase inhibitors were generated from formestane biotransformation. The resulting metabolites exhibited enhanced potency against aromatase and breast cancer cell lines compared to the parent compound.
Area of Science:
- Medicinal Chemistry
- Biotechnology
- Endocrinology
Background:
- Aromatase is a key enzyme in estrogen biosynthesis, making it a target for hormone-dependent breast cancer therapy.
- Formestane is a steroidal aromatase inhibitor with potential for developing more effective analogs.
Purpose of the Study:
- To generate novel steroidal aromatase inhibitors through biotransformation of formestane.
- To evaluate the biological activities of the resulting metabolites against aromatase and breast cancer cell lines.
Main Methods:
- Biotransformation of formestane using microbial cultures (Rhizopus oryzae and Beauveria bassiana).
- Structural elucidation of metabolites using spectroscopic techniques.
- Assay of aromatase inhibition and MCF-7 breast cancer cell activity.
Main Results:
- Biotransformation yielded known and one new steroidal metabolite.
- The new metabolite is 4,11α,17β-trihydroxyandrost-4-en-3-one.
- All identified metabolites demonstrated superior activity compared to formestane in both assays.
Conclusions:
- Microbial biotransformation is an effective strategy for generating potent steroidal aromatase inhibitors.
- The novel metabolite and other biotransformed products show promise for breast cancer treatment.
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