From Natural Sources to Synthetic Derivatives: The Allyl Motif as a Powerful Tool for Fragment-Based Design in Cancer Treatment

Since the beginning of history, natural products have been an abundant source of bioactive molecules for the treatment of different diseases, including cancer. Many allyl derivatives, which have shown anticancer activity both in vitro and in vivo in a large number of cancers, are bioactive molecules found in garlic, cinnamon, nutmeg, or mustard. In addition, synthetic products containing allyl fragments have been developed showing potent anticancer properties. Of particular note is the allyl derivative 17-AAG, which has been evaluated in Phase I and Phase II/III clinical trials for the treatment of multiple myeloma, metastatic melanoma, renal cancer, and breast cancer. In this Perspective, we compile extensive literature evidence with descriptions and discussions of the most recent advances in different natural and synthetic allyl derivatives that could generate cancer drug candidates in the near future.

Automated summary

Since ancient times, natural products have been a rich source of bioactive molecules for cancer treatment. Many allyl derivatives found in garlic, cinnamon, nutmeg, or mustard have shown anticancer activity in various cancers. Synthetic products with allyl fragments, such as 17-AAG, have also demonstrated potent anticancer properties in clinical trials. This Perspective compiles recent advances in natural and synthetic allyl derivatives, which have the potential to become future cancer drug candidates.