MOA Key Laboratory of Food Safety Evaluation/National Reference Laboratory of Veterinary Drug Residues, Huazhong Agricultural University, Wuhan, Hubei 430070, People’s Republic of China.
Curr Drug Metab. 2013 Jul;14(6):641-60. doi: 10.2174/1389200211314060002.
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.
三萜烯是一大类结构相关的毒素，主要由属于镰刀菌属的真菌产生。在三萜烯中，由于其广泛而高度毒性，A 型和 B 型最为关注。为了研究三萜烯的构效关系（SAR），本文总结了哺乳动物系统中三萜烯霉菌毒素的结构特征与生物效应之间的关系。C-9-C-10 之间的双键和 12,13-环氧环是三萜烯毒性的必需结构特征。去除这些基团会导致毒性完全丧失。C-3 上的羟基增强了三萜烯的毒性，而当 C-3 被氢或乙酰氧基取代时，这种活性逐渐降低。C-4 上的羟基基团略微促进较低的毒性，而在相同位置的乙酰氧基基团则略有降低毒性。如果 C-4 上的取代基从乙酰氧基变为 C-4 上的羟基或氢，则 B 型三萜烯的毒性降低。与 C-4 上的乙酰氧基相比，C-15 上的羟基和氢基团降低了三萜烯的毒性。当 C-4 和 C-15 之间存在大环环时，三萜烯的毒性增加。在 C-8 位置，C-8 上的含氧取代对于三萜烯的毒性是必需的，表明当取代基从异戊酰氧基通过氢变为羟基时，毒性降低。C-7-C-8 处的第二个环氧环降低了毒性，而一些大环三萜烯的 C-9-C-10 环氧化增加了活性。共轭三萜烯在动物体内水解后可以释放出其有毒前体，这是一个额外的潜在风险。三萜烯的 SAR 研究应该为更好地理解食品污染中三萜烯的化学和生物学特性提供一些关键信息。
