Background: Fumitremorgins are mycotoxins but can also inhibit cancer cells and
reverse their drug resistance.
Objective: The bioactivity of prenylated cyclo-Trp-Pro dipeptides and their derivatives concerning
their application in anti-cancer therapies will be discussed.
Methods: Reports on the discovery and assessment of this class of fungal compounds are
compiled from literature using Google Scholar and PubMed. The bioactivities of the natural
compounds are discussed with the aim of their improvement for cancer therapy.
Results: Although a number of compounds of this class have been found, only a minority of
them showed bioactivity in the applied bioassays. Fumitremorgins and related compounds are
active against various cancer cells but they are also mycotoxins. Some of these natural compounds
can arrest cancer cells in their cell cycle and some can block ABC-transporters and
reverse resistance in chemotherapy. Structure activity relationships have been deduced leading
to the prediction of highly active compounds. Several easily accessible derivatives of
these natural products have been discovered being highly selective and non-toxic.
Conclusion: Sophisticated screening methods, high throughput screening, metabolic engineering,
and synthetic biology are novel and promising technologies for the search for highly
active drugs. Rapid gene sequencing in combination with engineered biosynthetic pathways
should contribute substantially to novel pharmaceutics.