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Synthesis, Cytotoxicity, and Pro‐Apoptosis Activity of Etodolac Hydrazide Derivatives as Anticancer Agents
Author(s) -
Çıkla Pelin,
Özsavcı Derya,
BingölÖzakpınar Özlem,
Şener Azize,
Çevik Özge,
ÖzbaşTuran Suna,
Akbuğa Jülide,
Şahin Fikrettin,
Küçükgüzel Ş. Güniz
Publication year - 2013
Publication title -
archiv der pharmazie
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.468
H-Index - 61
eISSN - 1521-4184
pISSN - 0365-6233
DOI - 10.1002/ardp.201200449
Subject(s) - etodolac , chemistry , cytotoxicity , apoptosis , hydrazide , cell culture , cell growth , mtt assay , viability assay , stereochemistry , cancer cell , biochemistry , in vitro , pharmacology , cancer , biology , medicine , organic chemistry , genetics
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, 1 H NMR, 13 C 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‐tetrahydropyrano[3,4‐ 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 IC 50 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.