Synthesis and structure elucidation of 1-(2,5/3,5-difluorophenyl)-3-(2,3/2,4/2,5/3,4-dimethoxyphenyl)-2-propen-1-ones as anticancer agents

Abstract

The compounds titled 1-(2,5/3,5-difluorophenyl)-3-(2,3/2,4/2,5/3,4-dimethoxyphenyl)-2-propen-1-ones (1–8) were synthesized via Claisen-Schmidt condensation under basic condition. The chemical structure of the compounds were identified using several spectroscopic techniques such as 1H nuclear magnetic resonance (NMR), 13C NMR, 19F NMR, DEPT 90, DEPT 135, COSY, HMBC, and HMQC. Cytotoxic activities of the compounds were investigated towards several human tumour cell lines [gingival carcinoma (Ca9-22), oral squamous cell carcinoma derived from tongue (HSC-2)] and human normal oral cells [gingival fibroblasts (HGF), periodontal ligament fibroblasts (HPLF)]. Most of these compounds presented higher cytotoxicity than reference drug 5-fluorouracil while the compounds 7, [1-(3,5-difluorophenyl)-3-(2,5-dimethoxyphenyl)-2-propen-1-one)], and 2, [1-(2,5-difluorophenyl)-3-(2,4-dimethoxyphenyl)-2-propen-1-one], were presenting the best activity according to potency selectivity expression values. Type of cell death induced by compound 7 in both HSC-2 and Ca9-22 cells was investigated to understand mechanism of action of the compounds. The compound 7 produced cleaved products of PARP and caspase-3 were produced, suggesting the induction of apoptosis as a possible mechanism of action of the compounds characterized via activation of caspase-3 in both human oral squamous cell carcinomas.