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Synthesis and Cytotoxic Activities of Difluoro-Dimethoxy Chalcones

[ Vol. 17 , Issue. 10 ]


Cem Yamali, Halise Inci Gul*, Dilan Ozmen Ozgun, Hiroshi Sakagam, Naoki Umemura, Cavit Kazaz and Mustafa Gul   Pages 1426 - 1433 ( 8 )


Background: Although anticancer chemotherapeutics are available in markets, side effects related to the drugs in clinical use lead to researchers to investigate new drug candidates which are more safe, potent and selective than others. Chalcones are popular with their anticancer activities with the several reported mechanisms including inhibition of angiogenesis, inhibition of tubulin polymerization, and induction of apoptosis etc.

Objective: This study was focused on to synthesize of 1-(2,4/2,6-difluorophenyl)-3-(2,3/2,4/2,5/3,4- dimethoxyphenyl)-2-propen-1-ones (1-8) and investigate their cytotoxic properties with possible mechanism of action.

Method: The compounds were synthesized by Claisen-Schmidt condensation. The chemical structures were confirmed by 1H NMR, 13C NMR, DEPT, COSY, HMQC, HMBC, 19F NMR and HRMS. In vitro cytotoxic effects of the compounds against human tumour cell lines [gingival carcinoma (Ca9-22), oral squamous cell carcinoma (HSC-2)] and human normal oral cells [gingival fibroblasts (HGF), periodontal ligament fibroblasts (HPLF)] were evaluated via MTT test.

Results: All compounds had higher cytotoxicity than reference compound 5-Fluorouracil (5-FU). The compounds 3-7 had higher potency selectivity expression values (PSE) than 5-FU and PSE values of the compounds were over 100. All chalcone derivatives seem good candidates for further studies according to very remarkable and high PSE values.

Conclusion: It was clearly demonstrated that compound 7 can induce early apoptosis at a concentration of 10 µM and dose-dependent late apoptosis starting at 10 µM. Compound 7 induced cleavage of the apoptosis marker PARP. The results indicate that new chalcones reported here can promote apoptosis in human tumour cell lines.


Chalcone, cytotoxicity, dimethoxy, difluoro, potency selectivity expression, dental cells, PARP.


Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Ataturk University, Erzurum 25240, Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Ataturk University, Erzurum 25240, Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Agri Ibrahim Cecen University, Agri 04100, Division of Pharmacology, Meikai University School of Dentistry, Sakado, Saitama 350-0283, Division of Oral Biochemistry, Asahi University School of Dentistry, 1851 Hozumi, Mizuho City, Gifu 500-0296, Department of Chemistry, Faculty of Science, Ataturk University, Erzurum, Department of Physiology, Faculty of Medicine, Ataturk University, Erzurum

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