Synthesis and activity study of 4- hydroxyacetophenone- piperidine-Mannich bases

Al Mahamid, S.J. (2023). Synthesis and activity study of 4-hydroxyacetophenone-piperidine-Mannich bases. Yeditepe University Institute of Health sciences, Department of Pharmaceutical Chemistry, M.Sc. Thesis, Istanbul. In this thesis study, 13 new compounds bearing 1-[4-hydroxy-3-[(substituted-1-piperidinyl)methyl]phenyl]ethanone backbone were synthesized by Mannich reaction using conventional and microwave irradiation methods. In the first method, the target compounds were synthesized by reaction of the 4-hydroxyacetophenone, formaldehyde and some piperidine derivatives under reflux for seven hours in ethanol. In the second method, microwave radiation was applied on the 4-hydroxyacetophenone, formaldehyde and piperidine derivatives in 1, 4-dioxane with 15 min at 120°C and power 300 W. The results of two methods were compared. Structure elucidation of the 13 new compounds were confirmed by IR, 1H-NMR, 13C-NMR, and elementary analysis techniques. In addition, the cytotoxicity of synthesized compounds was tested on human breast cancer cell line (MCF7) by MTT assay. According to the activity result, 1-[4-hydroxy-3-[(4-phenylpiperidin-1-yl) methyl] phenyl]ethanone (compound 2) and 1-[4-hydroxy-3-[(4-cyano-4-phenylpiperidin-1-yl) methyl] phenyl]ethanone (compound 11) have high cytotoxic activity on MCF7 with IC50 values 22 and 29 µM, respectively. While compounds 1, 4, 5, 7, 9, 12 and 13 have moderate activity on the MCF7 cell line. Keywords: Cytotoxicity, piperidine, 4-hydroxyacetophenone, Mannich bases, microwave