A Water-Soluble Prodrug for the Heat Shock-Inducing Compound Withaferin A

Technology #ua09-006

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Leslie Gunatilaka
Professor, Natural Resources and the Environment
Dennis Ray
Professor, Plant Sciences
Yaming Xu
Research Associate, Natural Resources and the Environment
Kithsiri Wijeratne
Assistant Research Scientist, Natural Resources and the Environment
Managed By
Tod Mccauley

A Water-Soluble Prodrug for the Heat Shock-Inducing Compound Withaferin A.

Background: Preparations of the dried root of Withania somnifera, known as ashwagandha, have been used for thousands of years in the Ayurvedic medical tradition; such preparations have been shown to have anti-inflammatory, immunomodulatory, cardioprotective, antioxidant, anti-angiogenic and anti-cancer activity.

University of Arizona investigators discovered that when grown aeroponically, w.somnifera produces a novel class of withanolides that, in vitro, readily convert to Withaferin A and exhibit the anti-proliferative and anti-tumorigenic activities of Withaferin A. Experiments have shown that the novel compounds activate the heat shock response in fibroblasts and inhibit cell proliferation/survival in breast cancer cell lines.

The newly discovered compounds, however, are more water soluble than Withaferin A and, thus, may be more amenable to formulation for in vivo administration.

UA investigators have developed an economically viable and environmentally friendly method for producing and isolating large quantities of both Withaferin A and the novel withanolides. Aeroponic cultivation is a significant achievement as acquiring an abundant supply of starting material is often a significant hurdle in the development of drugs derived from natural products.

·       Withaferin A analogs may be used to develop antitumor agents with high solubility and low toxicity.

·       Large quantities of Withaferin A analogs can be produced cheaply with aeroponic cultivation of w.somnifera.
·       The compound can be delivered in a water soluble form that makes it an attractive potential cancer treatment.
·       Work is ongoing to determine if this compound has any of the other attractive bioactivities of ashwaganda.


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