Synthesis and biological evaluation of novel 3,6- amide and thioamide substituted- 2,3,4,9-tetrahydro-1H-carbazoles for anti-cancer activity

Herein, we report the synthesis of new compounds with demonstrated anticancer properties based on the 2,3,4,9-tetrahydro-1H-carbazole scaffold. The Fischer indolization method was used to close the heterocyclic motif. The synthesis method's scope and limitations were thoroughly assessed through a series of experiments. Biological assays revealed that two thioamide compounds exhibited significant anticancer activity against MCF-7, HTC116, and A596 cell lines. Comprehensive in vitro profiling included evaluation of cell cytotoxicity, morphological alterations, colony formation and cell adhesion in 3D cultures, cell cycle analysis, DNA damage induction, impact on mitochondria, and apoptosis. Ex ovo studies further demonstrated these compounds' potential to inhibit angiogenic processes. Our results indicate that the newly developed compounds activate processes leading to DNA damage and disruption of mitochondrial function.