title: Synthesis, cytotoxicity, and pro-apoptosis activity of etodolac hydrazide derivatives as anticancer agents.
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, (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.
authors.affiliation: Department of Pharmaceutical Chemistry, Marmara University, İstanbul, Turkey.
authors.forename: Pelin
authors.initials: P
authors.lastname: Çıkla
authors.forename: Derya
authors.initials: D
authors.lastname: Özsavcı
authors.forename: Özlem
authors.initials: Ö
authors.lastname: Bingöl-Özakpınar
authors.forename: Azize
authors.initials: A
authors.lastname: Şener
authors.forename: Özge
authors.initials: Ö
authors.lastname: Çevik
authors.forename: Suna
authors.initials: S
authors.lastname: Özbaş-Turan
authors.forename: Jülide
authors.initials: J
authors.lastname: Akbuğa
authors.forename: Fikrettin
authors.initials: F
authors.lastname: Şahin
authors.forename: Ş Güniz
authors.initials: ŞG
authors.lastname: Küçükgüzel
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3 / Q000378:metabolism; D002460:Cell Line; D045744:Cell Line, Tumor; D004305:Dose-Response Relationship, Drug; D017308:Etodolac / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D006835:Hydrazones / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D020128:Inhibitory Concentration 50; D008297:Male; D009369:Neoplasms / Q000188:drug therapy* / Q000473:pathology; D011471:Prostatic Neoplasms / Q000188:drug therapy / Q000473:pathology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D051381:Rats; D013057:Spectrum Analysis
chemical_list: D000970:Antineoplastic Agents; D006835:Hydrazones; D019253:Proto-Oncogene Proteins c-bcl-2; C000611994:etodolac hydrazone; D017308:Etodolac; D053148:Caspase 3