Synthesis of novel derivatives from machilin C/D as antiproliferative agents against triple negative breast cancer

Authors

• Alyson M. Ackerman, University of Kentucky
• Chibuzor Olewele, University of KentuckyFollow
• Bert C. Lynn, University of KentuckyFollow
• Samuel G. Awuah, University of KentuckyFollow

Abstract

Lignans are small polyphenolic compounds that play an active role in plant defense against pathogens and predators. Recently, lignan machilin D was reported to be effective as an anti-tumorigenic agent in triple negative breast cancer (TNBC) tumor-bearing mice. Previous studies have relied on plant-extracted material limiting scalability and diversification of the natural scaffold. Herein, we describe a generalizable one-pot synthesis of machilin D and its derivatives via an iron chloride-induced dimerization of isoeugenol. Employing this synthetic methodology allowed for a robust diversification campaign to access seven (7) new lignan derivatives of the machilin D family with superior anti-proliferative properties in 2D and 3D TNBC models. Overall, this work enables lignan natural product-based drug discovery as a platform to identify new probes to elucidate lignan targets in biology and therapeutics for aggressive cancers such as TNBC.

Document Type

Article

Publication Date

8-1-2025

Notes/Citation Information

Publisher Copyright: © 2025 The Authors

Digital Object Identifier (DOI)

10.1016/j.ejmcr.2025.100272

Archival?

Archival

Repository Citation

Ackerman, Alyson M.; Olewele, Chibuzor; Lynn, Bert C.; and Awuah, Samuel G., "Synthesis of novel derivatives from machilin C/D as antiproliferative agents against triple negative breast cancer" (2025). Chemistry Faculty Publications. 243.
https://uknowledge.uky.edu/chemistry_facpub/243