Abstract
Background and Objective: The growing prevalence of cancer and the resulting chemoresistance
exert a huge burden on healthcare systems and impose a great challenge to public health around the world. In
efforts to develop new chemotherapeutic agents for cancer treatment, a class of heterocyclic compounds i.e.
triazine-based molecules were investigated as anticancer agents.
Materials and Methods: New triazine hybrids of stilbene were synthesized and evaluated as anticancer agents
for cervical (HeLa) and breast (MCF-7) carcinoma cells. The compound (7e), sodium (E)-6,6'-(ethene-1,2-
diyl)bis(3-((4-chloro-6-((3-luorophenyl)amino)-1,3,5-triazin-2-yl)amino)benzenesulfonate) was found to be
most potent among synthesized derivatives and was explored further for detailed mechanistic studies.
Results: In a set comprised of twelve derivatives, compound 7e, sodium (E)-6,6'-(ethene-1,2-diyl)bis(3-((4-
chloro-6-((3-luorophenyl)amino)-1,3,5-triazin-2-yl)amino)benzenesulfonate) was found most potent inhibitor
for HeLa and MCF-7 cells.
Discussion: The present study has revealed that compound 7e may activate mitochondrial pathway of apoptosis
in HeLa and MCF-7 cells which was assessed by DNA binding studies, estimation of the release of Lactate
Dehydrogenase (LDH), fluorescence imaging, production of Reactive Oxygen Species (ROS) in cancer cells,
analysis of cell cycle by flow cytometry, change in Mitochondrial Membrane Potential (MMP) and activation of
caspase-9 and caspase-3.
Conclusion: Compound 7e may serve as a lead in designing new anticancer compounds based on stilbene scaffold.
Keywords:
Stilbene derivatives, cell cycle analysis, DNA binding studies, lactate dehydrogenase release, reactive oxygen species, mitochondrial
membrane potential, caspase-9, caspase-3.
Graphical Abstract
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