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Based on the use of s -triazine as a scaffold, we report here a new series of s -triazine Schiff base derivatives and their anti-proliferative activity against two cancer cell lines: human breast carcinoma (MCF-7), and colon cancer (HCT-116) compared with tamoxifen as a reference compound. Several derivatives exhibited growth inhibition activity in the sub-micromolar range. The results reveal that the s -triazine Schiff base derivatives showed varied activities and that the substituents on the s -triazine core have a great effect on the anti-proliferative activity. Compounds with a piperidino and benzylamino substituent on the s -triazine moiety 4b and 4c were most effective in both cell lines compared to the reference compound used. In addition, compound 4b has a para chlorine atom on the benzylidine residue, demonstrating the most potent activity with IC 50 values of 3.29 and 3.64 µM in MCF-7 and HCT-116, respectively. These results indicate that in general, the nature of the substituents on the triazine core and the type of substituent on the benzilyldene ring significantly influenced the anti-proliferative activity. The results obtained from the anti-proliferative activity and the molecular docking study indicate that s -triazine-hydrazone derivatives may be an excellent scaffold for the development of new anti-cancer agents.

Synthesis, Anti-proliferative Activity, and Molecular Docking Study of New Series of 1,3-5-Triazine Schiff Base Derivatives