Orellanine: From Fungal Origin to a Potential Future Cancer Treatment

Fungal metabolites represent an underutilizedresource in the developmentof novel anticancer drugs. This review will focus on the promisingfungal nephrotoxin orellanine, found in mushrooms including Cortinarius orellanus (Fools webcap). Emphasis will be placedon its historical significance, structural features, and associatedtoxicomechanics. Chromatographic methods for analysis of the compoundand its metabolites, its synthesis, and chemotherapeutic potentialare also discussed. Although orellanine's exceptional selectivityfor proximal tubular cells is well documented, the mechanics of itstoxicity in kidney tissue remains disputed. Here, the most commonlyproposed hypotheses are detailed in the context of the molecule'sstructure, the symptoms seen following ingestion, and its characteristicprolonged latency period. Chromatographic analysis of orellanine andits related substances remains challenging, while biological evaluationof the compound is complicated by uncertainty regarding the role ofactive metabolites. This has limited efforts to structurally refinethe molecule; despite numerous established methods for its synthesis,there is minimal published material on how orellanine's structuremight be optimized for therapeutic use. Despite these obstacles, orellaninehas generated promising data in preclinical studies of metastaticclear cell renal cell carcinoma, leading to the early 2022 announcementof phase I/II trials in humans.

Automated summary

Fungal metabolites, such as orellanine found in mushrooms, have potential as novel anticancer drugs. This review focuses on orellanine's historical significance, structural features, toxicomechanics, chromatographic analysis, synthesis, and chemotherapeutic potential. The toxicity mechanisms of orellanine in kidney tissue are still disputed, and its chromatographic analysis and biological evaluation face challenges. Despite these obstacles, orellanine has shown promising data in preclinical studies for metastatic clear cell renal cell carcinoma, leading to phase I/II trials in humans.