Polyphenolic natural products and natural product-inspired steroidal mimics as aromatase inhibitors

Medicinal Research Reviews
Alexander J Nielsen, James McNulty

Abstract

The discovery of biologically active polyphenolic natural products, including chalcones, stilbenes, flavanones, and isoflavones as steroidal mimics has proven to be a subject of considerable importance in medicine. Some of these natural compounds have been shown to modulate key human metabolic processes via steroidal hormone receptors, or to inhibit crucial enzymes involved in the biosynthesis of steroidal hormones themselves. Isoflavone polyphenolics such as genistein are well known for this "phytoestrogenic" biological activity. This review focuses on the ability of select polyphenolics and their synthetic derivatives to function as steroidal mimics in the inhibition of the enzyme aromatase, thereby lowering production of endogenous estrogen growth hormones. The discovery of potent, natural product-based aromatase inhibitors (AIs) as hit compounds has led to the introduction of steroidal-based irreversible inhibitors, such as exemestane and reversible AIs such as anastrozole and letrozole, now standard therapy in the treatment of estrogen receptor-positive breast cancer and other hormone related indications. Pursuit of this strategy over the last few decades has been largely successful although complications and challenges re...Continue Reading

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Citations

Mar 20, 2019·Journal of Asian Natural Products Research·Ni ChenKe Zhao
Nov 17, 2019·European Journal of Medicinal Chemistry·Marialuigia FantacuzziRosa Amoroso
Aug 24, 2021·ACS Applied Materials & Interfaces·Wentao FanSuquan Song
Jan 5, 2019·Chemical Research in Toxicology·Judy L BoltonBirgit M Dietz

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