Synthesis,Cytotoxicity, and Pro‐Apoptosis Activity of Etodolac Hydrazide Derivatives as Anticancer Agents |
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Authors: | Pelin Ç?kla Derya Özsavc? Özlem Bingöl‐Özakp?nar Azize ?ener Özge Çevik Suna Özba?‐Turan Jülide Akbu?a Fikrettin ?ahin ? Güniz Küçükgüzel |
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Institution: | 1. Department of Pharmaceutical Chemistry, Marmara University, ?stanbul, Turkey;2. Department of Biochemistry, Marmara University, ?stanbul, Turkey;3. Department of Biochemistry, Cumhuriyet University, Sivas, Turkey;4. Department of Pharmaceutical Biotechnology, Marmara University, ?stanbul, Turkey;5. Department of Genetics and Bioengineering, Yeditepe University, ?stanbul, Turkey |
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Abstract: | Etodolac hydrazide and a novel series of etodolac hydrazide‐hydrazones 3 – 15 and etodolac 4‐thiazolidinones 16 – 26 were synthesized in this study. The structures of the new compounds were determined by spectral (FT‐IR, 1H NMR, 13C NMR, HREI‐MS) methods. Some selected compounds were determined at one dose toward the full panel of 60 human cancer cell lines by the National Cancer Institute (NCI, Bethesda, USA). 2‐(1,8‐Diethyl‐1,3,4,9‐tetrahydropyrano3,4‐b]indole‐1‐yl)acetic acid(4‐chlorophenyl)methylene]hydrazide 9 demonstrated the most marked effect on the prostate cancer cell line PC‐3, with 58.24% growth inhibition at 10?5 M (10 µM). Using the MTT colorimetric method, compound 9 was evaluated in vitro against the prostate cell line PC‐3 and the rat fibroblast cell line L‐929, for cell viability and growth inhibition at different doses. Compound 9 exhibited anticancer activity with an IC50 value of 54 µM (22.842 µg/mL) against the PC‐3 cells and did not display any cytotoxicity toward the L‐929 rat fibroblasts, compared to etodolac. In addition, this compound was evaluated for caspase‐3 and Bcl‐2 activation in the apoptosis pathway, which plays a key role in the treatment of cancer. |
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Keywords: | Apoptosis Etodolac Hydrazide‐hydrazone PC‐3 prostate cancer cell line 4‐Thiazolidinone |
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