Department of Chemistry and Chemical Biology, Northeastern University, Boston, Massachusetts 02115, United States.
Center for Tropical and Emerging Global Diseases, University of Georgia, Athens, Georgia 30602, United States.
J Nat Prod. 2024 Feb 23;87(2):315-321. doi: 10.1021/acs.jnatprod.3c01019. Epub 2024 Jan 23.
Trichothecenes (TCNs) are a large group of tricyclic sesquiterpenoid mycotoxins that have intriguing structural features and remarkable biological activities. Herein, we focused on three TCNs (anguidine, verrucarin A, and verrucarol) and their ability to target both the blood and liver stages of species, the parasite responsible for malaria. Anguidine and verrucarin A were found to be highly effective against the blood and liver stages of malaria, while verrucarol had no effect at the highest concentration tested. However, these compounds were also found to be cytotoxic and, thus, not selective, making them unsuitable for drug development. Nonetheless, they could be useful as chemical probes for protein synthesis inhibitors due to their direct impact on parasite synthesis processes.
三萜烯类(TCNs)是一大类三环倍半萜霉菌毒素,具有引人入胜的结构特征和显著的生物活性。在此,我们重点研究了三种 TCNs(安古定、疣孢菌素 A 和疣孢菌素)及其靶向疟原虫(引起疟疾的寄生虫)的血期和肝期的能力。安古定和疣孢菌素 A 被发现对疟疾的血期和肝期均具有高度疗效,而在测试的最高浓度下,疣孢菌素则没有效果。然而,这些化合物也被发现具有细胞毒性,因此不具有选择性,使其不适合药物开发。尽管如此,由于它们对寄生虫合成过程的直接影响,它们可以作为蛋白质合成抑制剂的化学探针,具有一定的应用价值。