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: Y Sugita, H Hosoya, K Terasawa, I Yokoe, S Fujisawa, H Sakagami
• Journal: Anticancer research (Anticancer Res) 2001 Jul-Aug Vol. 21 Issue 4A Pg. 2629-32 ISSN: 0250-7005 [Print] Greece
• PMID: 11724331 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents
• Benzothiepins

Topics

• Antineoplastic Agents (chemical synthesis, toxicity)
• Benzothiepins (chemical synthesis, toxicity)
• Carcinoma, Squamous Cell (drug therapy)
• Drug Screening Assays, Antitumor
• Fibroblasts (cytology, drug effects)
• Gingiva (cytology, drug effects)
• HL-60 Cells (drug effects)
• Humans
• Mouth Neoplasms (drug therapy)
• Salivary Gland Neoplasms (drug therapy)
• Structure-Activity Relationship
• Tumor Cells, Cultured