Plant-derived withanolides are a family of naturally occurring chemicals that have long been the subject of cancer research because of their capacity to stop the development of cancer cells, cause cell death, and stop them from spreading. These substances are crucial for creating novel cancer therapies. Research and the development of new treatments have been hampered, nevertheless, by the challenge of extracting sufficient amounts of these chemicals from plants.
Moffitt Cancer Center researchers published their findings in the journal, Science Advances.
Our new synthesis route represents a major step forward in the field of withanolide chemistry,
By enabling the diversifiable production of these compounds on a gram scale, we can now support more extensive biological research and medicinal chemistry efforts.
Justin M. Lopchuk, Ph.D.
One of the novel synthesis’s key features is a bioinspired photooxygenation-allylic hydroperoxide rearrangement sequence that makes it easier to add functional groups in the synthesis’s final stages. This method permits the quick creation of many distinct withanolides from the same synthesis while guaranteeing scalability. Additionally, it eliminates the need for plant extraction, which is laborious and constrained by the chemicals’ inherent abundance.
Thanks to the scalable synthesis of withanolides, researchers can now create these chemicals in bigger quantities, which will speed up the development of withanolide-based cancer therapies and enable new research. Withanolides work on many cellular pathways, in contrast to traditional therapies that target a single route. To strengthen the body’s defences against cancer, they can disrupt the growth of cancer cells, harm the cellular structures of cancer cells, and alter the immune system. Furthermore, by increasing the sensitivity of cancer cells to radiation and chemotherapy, they may improve the efficacy of cancer therapies. They have demonstrated effectiveness against a variety of cancer types, such as prostate, lung, breast, and colon.
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Their capability to overcome drug resistance is another important factor. Over time, conventional therapies may cause cancer cells to become resistant. However, because of their distinct modes of action, withanolides may be able to overcome this resistance and continue to be helpful in situations where other treatments are ineffective.
Now that we have a reliable method to produce withanolides, we can focus our studies on creating new therapeutics to help cancer patients.
Justin M. Lopchuk, Ph.D.
Source: Moffitt Cancer Center News
Journal Reference: Che, Wen, et al. “Divergent Synthesis of Complex Withanolides Enabled by a Scalable Route and Late-stage Functionalization.” Science Advances, 2024, https://doi.org/adp9375.
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