title: Cytotoxic activity of 2-aminomethylene-3(2H)-benzofuranones against human oral tumor cell lines.
abstract: A total of 23 newly-synthesized 2-aminomethylene-3(2H)-benzofuranone and structurally-related compounds were compared for their cytotoxic activity against both normal (human gingival fibroblast HGF) and tumor cells (human oral squamous cell lines HSC-2, HSC-3 and human salivary gland tumor cells HSG). There was a significant variability of drug sensitivity among the oral tumor cell lines. In general, HSC-2 cells were the most sensitive, followed by HSG cells, while HSC-3 cells were the most resistant. HGF normal cells were highly resistant to all compounds, suggesting their tumor-specific cytotoxic action. The cytotoxic activity of the compounds with morpholine, 1-methylpiperazine or piperidine structure was generally elevated by the introduction of fluorine, but not chlorine and methoxy functional groups, to the benzofuranone structure, whereas that of compounds attached by 1-phenylpiperazine or 1-(2-pyridyl)piperazine was rather reduced. The most active compounds induced internucleosomal DNA fragmentation in human promyelocytic leukemia HL-60 cells, but not in HSG, further confirming that oral tumor cell lines are resistant to DNase digestion.
authors.affiliation: Faculty of Pharmaceutical Sciences, Josai University, Sakado, Saitama, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Terasawa
authors.forename: Y
authors.initials: Y
authors.lastname: Sugita
authors.forename: I
authors.initials: I
authors.lastname: Yokoe
authors.forename: S
authors.initials: S
authors.lastname: Fujisawa
authors.forename: H
authors.initials: H
authors.lastname: Sakagami
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D001572:Benzofurans / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy*; D004354:Drug Screening Assays, Antitumor; D005347:Fibroblasts / Q000187:drug effects; D005881:Gingiva / Q000166:cytology / Q000187:drug effects; D006801:Humans; D009062:Mouth Neoplasms / Q000188:drug therapy*; D010880:Piperidines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D012468:Salivary Gland Neoplasms / Q000188:drug therapy; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured
chemical_list: D000970:Antineoplastic Agents; D001572:Benzofurans; D010880:Piperidines