Ashimbayeva Meruyert, Szakonyi Zsolt, Adekenov Sergazy M, Szemerédi Nikoletta, Spengler Gabriella, Le Tam Minh
Institute of Pharmaceutical Chemistry, University of Szeged, Eötvös u. 6, H-6720 Szeged, Hungary.
JSC Research and Production Center "Phytochemistry", Karaganda 100009, Kazakhstan.
Biomolecules. 2025 Apr 14;15(4):578. doi: 10.3390/biom15040578.
Grossheimin, a guaiane-type sesquiterpene lactone, displayed a diverse range of biological activities, including anticancer, anti-inflammatory and antimicrobial effects. Various amino analogues of grossheimin were prepared through a Michael addition at its highly active α-methylene-γ-lactone motif. On the other hand, grossheimin was reduced to diol, which was then subjected to nucleophilic addition or acetylation to introduce heteroatoms associated with oxygen, sulfur or nitrogen functionalities. All of the synthesised Michael and acetylated adducts were evaluated for their in vitro cytotoxic action on human colon adenocarcinoma lines, including Colo205 and Colo320. The bioassay results indicated that the acetylated adducts displayed a potent cytotoxic effect compared to grossheimin, the parent molecule. A docking study was also performed to exploit the observed results.
格罗斯海明（Grossheimin）是一种愈创木烷型倍半萜内酯，具有多种生物活性，包括抗癌、抗炎和抗菌作用。通过在其高活性的α-亚甲基-γ-内酯基序上进行迈克尔加成反应，制备了格罗斯海明的各种氨基类似物。另一方面，格罗斯海明被还原为二醇，然后进行亲核加成或乙酰化反应，以引入与氧、硫或氮官能团相关的杂原子。对所有合成的迈克尔加成产物和乙酰化加合物进行了体外细胞毒性作用评估，受试细胞系为人结肠腺癌细胞系，包括Colo205和Colo320。生物测定结果表明，与母体分子格罗斯海明相比，乙酰化加合物显示出强大的细胞毒性作用。还进行了对接研究以探究观察到的结果。
