Synthesis and Antiproliferative Effects of Grossheimin-Derived Aminoanalogues
Meruyert Ashimbayeva,
Zsolt Szakonyi,
Sergazy M. Adekenov,
Nikoletta Szemerédi,
Gabriella Spengler,
Tam Minh Le
Affiliations
Meruyert Ashimbayeva
Institute of Pharmaceutical Chemistry, University of Szeged, Eötvös u. 6, H-6720 Szeged, Hungary
Zsolt Szakonyi
Institute of Pharmaceutical Chemistry, University of Szeged, Eötvös u. 6, H-6720 Szeged, Hungary
Sergazy M. Adekenov
JSC Research and Production Center “Phytochemistry”, Karaganda 100009, Kazakhstan
Nikoletta Szemerédi
Department of Medical Microbiology, Albert Szent-Györgyi Health Center and Albert Szent-Györgyi Medical School, University of Szeged, Semmelweis utca 6, H-6725 Szeged, Hungary
Gabriella Spengler
Department of Medical Microbiology, Albert Szent-Györgyi Health Center and Albert Szent-Györgyi Medical School, University of Szeged, Semmelweis utca 6, H-6725 Szeged, Hungary
Tam Minh Le
Institute of Pharmaceutical Chemistry, University of Szeged, Eötvös u. 6, H-6720 Szeged, Hungary
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.
