Conjugation of substituted ferrocenyl to thiadiazine as apoptosis-inducing agents targeting the Bax/Bcl-2 pathway

Ferrocene compounds are a class of biologically active compounds that has antitumour and antifungal properties. This study investigated the induction of apoptosis in human fibrosarcoma cells (HT1080) after treatment with a series of 6-ferrocenyl-3-subsituted7H-1,2,4-triazolo[3,4-b]- 1,3,4-thiadiazine (FTFs). We found that FTFs could suppress the viability of HT1080 cells. Cell cycle analysis showed that proliferative inhibition of HT1080 cells occurred through apoptosis, as the cells were blocked in G1 phase. Moreover, mitochondrial membrane staining assay demonstrated that FTFs exposure significantly decreased mitochondrial membrane potential. Finally, under the stress of FTFs, Bax/Bcl-2 ratio in HT1080 cells was significantly increased. These results suggested that FTFs-induced apoptosis in HT1080 cells may work dependent on a Bax/Bcl-2 pathway.

The cyclization of 4-amino-5-substituted 1,2,4-triazol-3-thione with α-halogenocarbonyl compounds has been the most useful method for the formation of the 1,2,4-triazolo[3,4-b]-1,3,4-thiadiazine ring system. Figure optionsDownload as PowerPoint slideHighlights
► Thiadiazine derivatives could suppress the viability of HT1080 cells.
► Proliferative inhibition of HT1080 cells occurred through apoptosis.
► Thiadiazine derivatives exposure decreased mitochondrial membrane potential.
► Bax/Bcl-2 ratio in cells was increased under the stress of Thiadiazine derivatives.