1-(3-Aminomethyl-4-hydroxyphenyl)-3-pyridinyl-2-propen-1-ones: A novel group of tumour-selective cytotoxins

Abstract

Two series of 1-(3-aminomethyl-4-hydroxyphenyl)-3-pyridinyl-2-propen-1-ones, designed as novel cytotoxins, were synthesized. The compounds had low CC₅₀ values in the micromolar range against HL-60 promyelocytic leukemic cells and HSC-2, HSC-3 and HSC-4 oral squamous cell carcinomas. The CC₅₀ values of these compounds were higher towards non-malignant HGF (gingival fibroblasts), HPC (pulp cells), and HPLF (periodontal ligament fibroblasts) cells, which reveals the tumour-selectivity of these enones. A representative compound 4c caused cleavage of PARP1 in HSC-2 cells but not in HGF cells, which may be a contributing factor to the tumour-selectivity.

Keywords::

• Mannich bases
• azachalcones
• cytotoxicity
• molecular modelling
• PARP1

Acknowledgments

This study was supported by the Research Foundation of Ataturk University (Project Number: 2009/317, 2010/166) Erzurum, Turkey.

Declaration of interest

The authors report no conflict of interest and are responsible for the contents and writing of the paper.