Design and synthesis of novel 1,2,4-triazolo[4,3-b]pyridazine derivatives with anti-cancer activity

Novel 1,2,4-triazolo[4,3-b]pyridazine derivatives (7a-d, 8a-m and 9a-i) were designed and synthesized in good to moderate yields. The synthesized compounds were characterized by spectroscopic studies (NMR and IR) and the fluorine coupled 13C NMR data for each synthesized series have also been explained. The compounds were evaluated for their in-vitro anti-proliferative activity against K562, MV4-11, G361 and HCC827 human cancer cell lines. Almost all the synthesised compounds were active against MV4-11 below 25 & mu;M, especially 8l which showed activity with IC50 of 1.5 & mu;M. Furthermore, compound 8l displayed anticancer activity against all four cancer cell lines tested with IC50 values ranging from 1.5 to 7.6 & mu;M. In general, most of the compounds did not show any significant anti-proliferative activity against K562, G361 and HCC827 cells. Preliminary investigation of their effect on proliferation and viability of MV4-11 cells was carried out with 8l and the results indicate that the cells undergo a cell death with biochemical signs of apoptosis.

Automated summary

A series of novel 1,2,4-triazolo[4,3-b]pyridazine derivatives were designed and synthesized, with good to moderate yields. Spectroscopic studies (NMR and IR) confirmed the synthesis of the compounds, and the fluorine coupled 13C NMR data were explained. The compounds were tested for their in-vitro anti-proliferative activity against four human cancer cell lines, with compound 8l showing the most promising results.