Trichothecenes comprise a large family of structurally related toxins mainly produced by fungi belonging to the genus
Fusarium. Among trichothecenes, type A and type B are of the most concern due to their broad and highly toxic nature. In order to address
structure-activity relationships (SAR) of trichothecenes, relationships between structural features and biological effects of trichothecene
mycotoxins in mammalian systems are summarized in this paper. The double bond between C-9-C-10 and the 12,13-epoxide ring
are essential structural features for trichothecene toxicity. Removal of these groups results in a complete loss of toxicity. A hydroxyl
group at C-3 enhances trichothecene toxicity, while this activity decreases gradually when C-3 is substituted with either hydrogen or an
acetoxy group. The presence of a hydroxyl group at C-4 promotes slightly lower toxicity than an acetoxy group at the same position. The
toxicity for type B trichothecenes decreases if the substituent at C-4 is changed from acetoxy to hydroxyl or hydrogen at C-4 position.
The presence of hydroxyl and hydrogen groups on C-15 decreases the trichothecene toxicity in comparison with an acetoxy group attached
to this carbon. Trichothecenes toxicity increases when a macrocyclic ring exists between the C-4 and C-15. At C-8 position, an
oxygenated substitution at C-8 is essential for trichothecene toxicity, indicating a decrease in the toxicity if substituent change from
isovaleryloxy through hydrogen to the hydroxyl group. The presence of a second epoxy ring at C-7-C-8 reduces the toxicity, whereas epoxidation
at C-9-C-10 of some macrocyclic trichothecenes increases the activity. Conjugated trichothecenes could release their toxic precursors
after hydrolysis in animals, and present an additional potential risk. The SAR study of trichothecenes should provide some crucial
information for a better understanding of trichothecene chemical and biological properties in food contamination.
Keywords: Structure-activity relationship (SAR), T-2 toxin, trichothecenes, mycotoxin, toxicity, metabolism.
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