Synthesis and cytotoxicity of 2-methyl-1-substituted-imidazo [4,5-g]quinoline-4,9-dione and 7,8-dihydro-10H-[1,4]oxazino[3 ',4 ': 2,3]imidazo[4,5-g]quinoline-5,12-dione derivatives

2-Methyl-1-substituted-imidazo[4,5-g]quinoline-4,9-diones and 7,8-dihydro-1 0H-[1,4]oxazino -[3',4':2,3]imidazo[4,5-g]quinoline-5,12-dione (19) derivat ives have been synthesized from 6,7-dichloro-5,8-qninolinedione for develop ing the new anticancer drugs. Our study on the cytotoxicity of imidazoquino linedione derivatives has revealed that 7,8-dihydro-10H-[1,4]oxazino-[3',4' :2,3]imidazo [4,5-g]quinoline-5,12-dione (19), a tetracyclic heteroquinone analogue, exhibited high cytotoxicity on human colon tumor cell (HCT 15) in vitro SRB assay. The IC50 value of this compound was 0.026 mu g/mL whereas those of doxorubicin and cisplatin were 0.023 mu g/mL and 1.482 mu g/mL, r espectively. Meanwhile compounds 5-7 and 12 in the series of 1-substituted- imidazoquinolinediones showed relatively good activity on human brain tumor cell lines (XF 498). (C) 2000 Elsevier Science Ltd. All rights reserved.