Novel Cytotoxic Phenanthro-triazine-3-thiol Derivatives as Potential DNA Intercalators and Bcl-2 Inhibitors.

Novel phenanthro-triazine-3-thiol derivatives were designed as potential DNA intercalators and Bcl-2 inhibitors. After being synthesized, the compounds were evaluated for their cytotoxic activity against MOLT-4 (human acute lymphoblastic leukemia) and MCF-7 (human breast adenocarcinoma) cells by MTT assay. (bearing hydrogen substitution) was the most potent derivative against MOLT-4 with an IC value of 7.1 ± 1.1 μM, whereas (bearing phenyl substitution) demonstrated considerable cytotoxicity against MCF-7 with an IC value of 15.4 ± 2.9 μM. Compounds , , and exhibited moderate cytotoxic effects. Furthermore, to confirm the potential DNA intercalation and Bcl-2 inhibitory activities of phenanthro-triazine scaffolds, molecular docking analysis was performed. Molecular docking studies indicated that these compounds not only bind to DNA by intercalation mainly through stacking interactions but also are well accommodated in the active site of Bcl-2. Therefore, and having phenanthro-triazine-3-thiol scaffold could be presented as cytotoxic agents with dual DNA intercalation and Bcl-2 inhibitory activities.