Title:Macrocyclic trichothecenes as antifungal and anticancer compounds
Volume: 23
Issue: 1
Author(s): Maira Peres de Carvalho, Herbert Weich and Wolf-Rainer Abraham
Affiliation:
Keywords:
Sesquiterpenes, macrocyclic trichothecenes, cytotoxicity, anti-cancer activity, roridin, mode of action,
structure-activity relationships.
Abstract: Trichothecenes are sesquiterpenoid metabolites produced by fungi and species of
the plant genus Baccharis, family Asteraceae. They comprise a tricyclic core with an epoxide
at C-12 and C-13 and can be grouped into non-macrocyclic and macrocyclic compounds.
While many of these compounds are of concern in agriculture, the macrocyclic metabolites
have been evaluated as antiviral, anti-cancer, antimalarial and antifungal compounds. Some
known cytotoxic responses on eukaryotic cells include inhibition of protein, DNA and RNA syntheses, interference
with mitochondrial function, effects on cell division and membranes. These targets however have
been elucidated essentially employing non-macrocyclic trichothecenes and only one or two closely related
macrocyclic compounds. For several macrocyclic trichothecenes high selectivity against fungal species and
against cancer cell lines have been reported suggesting that the macrocycle and its stereochemistry are of crucial
importance regarding biological activity and selectivity. This review is focused on compounds belonging
to the macrocyclic type, where a cyclic diester or triester ring binds to the trichothecane moiety at C-4 and C-
15 leading to natural products belonging to the groups of satratoxins, verrucarins, roridins, myrotoxins and
baccharinoids. Their biological activities, cytotoxic mechanisms and structure-activity relationships (SAR)
are discussed. From the reported data it becomes evident that even small changes in the molecules can lead to
pronounced effects on biological activity or selectivity against cancer cells lines. Understanding the underlying
mechanisms may help to design highly specific drugs for cancer therapy.
