Faisal Rashid, Aamer Saeed and Jamshed Iqbal* Pages 793 - 802 ( 10 )
<P>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. </P><P> 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. </P><P> 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. </P><P> 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. </P><P> Conclusion: Compound 7e may serve as a lead in designing new anticancer compounds based on stilbene scaffold.</P>
Stilbene derivatives, cell cycle analysis, DNA binding studies, lactate dehydrogenase release, reactive oxygen species, mitochondrial membrane potential, caspase-9, caspase-3.
Centre for Advanced Drug Research, COMSATS University Islamabad, Abbottabad Campus, Abbottabad-22060, Department of Chemistry, Quaid-i-Azam University, Islamabad, Centre for Advanced Drug Research, COMSATS University Islamabad, Abbottabad Campus, Abbottabad-22060