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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

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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.

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Acknowledgements

This research work was supported by Ataturk University Research Found, Turkey (Project No: 2015/078). Gul HI thanks to Dr. Yusuf Ozkay (Faculty of Pharmacy, Anadolu University, Eskisehir, Turkey) and MSc. Serkan Levent (Faculty of Pharmacy, Anadolu University, Eskisehir, Turkey) for HRMS analyses.

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Authors and Affiliations

  1. Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Ataturk University, Erzurum, Turkey

    Cem Yamali & Halise Inci Gul

  2. Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Agri Ibrahim Cecen University, Agri, Turkey

    Dilan Ozmen Ozgun

  3. Meikai University Research Institute of Odontology (M-RIO), Meikai University School of Dentistry, Sakado, Saitama, 350-0283, Japan

    Hiroshi Sakagami & Noriyuki Okudaira

  4. Department of Chemistry, Faculty of Science, Ataturk University, Erzurum, Turkey

    Cavit Kazaz

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  1. Cem Yamali
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  2. Dilan Ozmen Ozgun
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  3. Halise Inci Gul
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  4. Hiroshi Sakagami
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  5. Cavit Kazaz
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  6. Noriyuki Okudaira
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Correspondence to Halise Inci Gul.

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Yamali, C., Ozgun, D.O., Inci Gul, H. et al. 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. Med Chem Res 26, 2015–2023 (2017). https://doi.org/10.1007/s00044-017-1911-0

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