AI Article Synopsis
- - Cancer is a major global health issue, and there's a pressing need for new, effective anticancer treatments due to limitations of current drugs.
- - Epidithiodiketopiperazine (ETP) alkaloids, derived from fungi and characterized by their unique sulfur structures, show significant anticancer activity by impacting various cancer-related pathways and processes.
- - The review discusses the anticancer potential of ETP alkaloids, how modifying their structures can enhance their effectiveness, and the development of synthetic methods to overcome supply challenges from natural sources.
Article Abstract
Cancer has become a grave health crisis that threatens the lives of millions of people worldwide. Because of the drawbacks of the available anticancer drugs, the development of novel and efficient anticancer agents should be encouraged. Epidithiodiketopiperazine (ETP) alkaloids with a 2,5-diketopiperazine (DKP) ring equipped with transannular disulfide or polysulfide bridges or S-methyl moieties constitute a special subclass of fungal natural products. Owing to their privileged sulfur units and intriguing architectural structures, ETP alkaloids exhibit excellent anticancer activities by regulating multiple cancer proteins/signaling pathways, including HIF-1, NF-κB, NOTCH, Wnt, and PI3K/AKT/mTOR, or by inducing cell-cycle arrest, apoptosis, and autophagy. Furthermore, a series of ETP alkaloid derivatives obtained via structural modification showed more potent anticancer activity than natural ETP alkaloids. To solve supply difficulties from natural resources, the total synthetic routes for several ETP alkaloids have been designed. In this review, we summarized several ETP alkaloids with anticancer properties with particular emphasis on their underlying mechanisms of action, structural modifications, and synthetic strategies, which will offer guidance to design and innovate potential anticancer drugs.
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| http://dx.doi.org/10.1016/j.bioorg.2023.106642 | DOI Listing |
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