title: Cytotoxic activity of benzothiepins against human oral tumor cell lines.
abstract: A total of 11 newly synthesized benzothiepins and structurally-related compounds were investigated for cytotoxic activity against both normal and tumor cells. All these compounds showed higher cytotoxic activity against three human oral tumor cell lines (HSC-2, HSC-3, HSG) than against normal human gingival fibroblast (HGF), suggesting tumor-specific cytotoxic action. In general, 3,4-dihydro-1-benzothiepin-5(2H)-ones [1-6] showed higher cytotoxic activity than 2,3-dihydro-1-benzothiepins [7-11]. Compounds 4 (4-bromo-3,4-dihydro-2-(2-oxo-2-phenylethyl)-1-benzothiepin-5(2H)-one), 5 (4-bromo-3,4-dihydro-2-(2-oxopropyl)-1-benzothiepin-5(2H)-one) and 6 (4-bromo-3,4-dihydro-2-[1-(methoxycarbonyl)-1-methylethyl]-1-benzothiepin-5(2H)-one), showed higher cytotoxic activity than compounds 1, 2 and 3, respectively, which had Cl instead of Br at C-4 position. Agarose gel electrophoresis demonstrated that these compounds induced large DNA fragments in oral tumor cells, whereas they produced smear pattern of smaller DNA fragments in human promyelocytic leukemia cells HL-60. These data suggest the medicinal efficacy of benzothiepins.
authors.affiliation: Faculty of Pharmaceutical Sciences, Josai University, Sakado, Saitama, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Sugita
authors.forename: H
authors.initials: H
authors.lastname: Hosoya
authors.forename: K
authors.initials: K
authors.lastname: Terasawa
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 / Q000633:toxicity*; D001582:Benzothiepins / Q000138:chemical synthesis / Q000633:toxicity*; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy; D004354:Drug Screening Assays, Antitumor; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects; D005881:Gingiva / Q000166:cytology / Q000187:drug effects; D018922:HL-60 Cells / Q000187:drug effects; D006801:Humans; D009062:Mouth Neoplasms / Q000188:drug therapy*; D012468:Salivary Gland Neoplasms / Q000188:drug therapy; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured
chemical_list: D000970:Antineoplastic Agents; D001582:Benzothiepins