A C-ring regioisomer of the marine alkaloid meridine exhibits selective invitro cytotoxicity for solid tumours

9-Hydroxybenzo[b]pyrido[4,3,2-de](1,10)-phenantrolin-8-one (1), a regioisom er of the marine alkaloid meridine, was synthesized from 5,8-dimethoxy-6-ni tro-4(1H)-quinolinone in eight steps and 23% overall yield. A shorter route was also investigated, based on the hetero Diels-Alder reaction between o- nitrocinnamaldehyde dimethylhydrazone and 4-halogen-6-bromo-5,8-quinolinequ inones followed by reductive cyclization onto the C-5 carbonyl of the quino ne. Compound 1 showed a remarkable in vitro cytotoxicity, with a pattern of selectivity towards solid rumours that is not found in the reference alkal oid, the activity against the human lung carcinoma (A-549) being particular ly noteworthy. The activities of meridine and compound 1 as inhibitors of t opoisomerase II were also significantly different. (C) 2001 Elsevier Scienc e Ltd. All rights reserved.