Synthesis, cytotoxicity, and pro-apoptosis activity of etodolac hydrazide derivatives as anticancer agents

Cikla P., ÖZSAVCI D., BİNGÖL ÖZAKPINAR Ö., ŞENER A., Cevik O., ÖZBAŞ TURAN S., ...Daha Fazla

Archiv der Pharmazie, cilt.346, sa.5, ss.367-379, 2013 (SCI-Expanded) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 346 Sayı: 5
  • Basım Tarihi: 2013
  • Doi Numarası: 10.1002/ardp.201200449
  • Dergi Adı: Archiv der Pharmazie
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Sayfa Sayıları: ss.367-379
  • Anahtar Kelimeler: Apoptosis, Etodolac, Hydrazide-hydrazone, PC-3 prostate cancer cell line, 4-Thiazolidinone, NATIONAL-CANCER-INSTITUTE, ANTIMYCOBACTERIAL ACTIVITY, BIOLOGICAL-ACTIVITIES, POTENTIAL ANTITUMOR, IN-VITRO, DRUG DISCOVERY, CYCLOOXYGENASE-2, PROSTATE, INHIBITOR, CELLS
  • Marmara Üniversitesi Adresli: Evet

Özet

Etodolac hydrazide and a novel series of etodolac hydrazide-hydrazones 315 and etodolac 4-thiazolidinones 1626 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-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 105M (10 mu M). 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 mu M (22.842 mu g/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.