Cytotoxic activity of benzothiepins against human oral tumor cell lines

A total of 11 newly synthesized benzothiepins and structurally-related comp ounds were investigated for cytotoxic activity against both normal and tumo r 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 g eneral, 3,4-dihydro-1-benzothiepin5(2H)-ones [1-6] showed higher cytotoxic activity than 2,3dihydro-1-benzothiepins [7-11]. Compounds 4 (4-bromo-3,4di hydro-2-(2-oxo-2-phenylethyl)-1-benzothiepin-5(2H)-one), 5 (4-bromo-3,4-dih ydro-2-(2-oxopropyl)-1-benzothiepin-5(2H)one) and 6 (4-bromo-3,4-dihydro-2- [1-(methoxycarbonyl)-1methylethyl]-1-benzothiepin-5(2H)-one), showed higher Cytotoxic activity than compounds 1, 2 and 3, respectively, which had Cl i nstead of Br at C-4 position. Agarose gel electrophoresis demonstrated that these compounds induced large DNA fragments in oral tumor cells, whereas t hey produced smear pattern of smaller DNA fragments in human promyelocytic leukemia cells HL-60. These data suggest the medicinal efficacy of benzothi epins.