Development of 1,2,3-Triazolopyridazinone Derivatives as Potential Caspase 3 and Apoptosis Inducers: Design, Synthesis and Anticancer Activity Studies

Abstract

Herein, the synthesis, anticancer activity and apoptotic pathways of 1,2,3-triazolopyridazinones compounds, which are similar to DNA bases not previously found in the literature have been investigated. To achieve this goal, it is designed the hybrid molecules combining triazole and pyridazinone/pyridazithione structures, bearing a lipophilic group (benzyl/phenyl) at the one position and benzene with electron withdrawing or donating groups at five positions, with high pharmacophoric properties on the same scaffold structure. The representative compounds in this series 5a, 5c, 6a and 8c exhibited higher anticancer activity than other compounds and cisplatin control against breast (MCF-7) and lung (A549) cell lines. These compounds were less toxic when tested against the noncancerous L929 cell line. In addition, the apoptotic effect mechanisms of these compounds were confirmed by AO/EB staining and caspase 3 activity results. These findings indicate that some derivatives of these compounds could be effective therapeutic agents for the treatment of cancer disease with an apoptosis-promoting.