A C-Ring Regioisomer of the Marine Alkaloid Meridine Exhibits Selective In Vitro Cytotoxicity for Solid Tumours Original Research Article

9-Hydroxybenzo[b]pyrido[4,3,2-de](1,10)-phenantrolin-8-one (), a regioisomer of the marine alkaloid meridine, was synthesized from 5,8-dimethoxy-6-nitro-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-quinolinequinones followed by reductive cyclization onto the C-5 carbonyl of the quinone. Compound showed a remarkable in vitro cytotoxicity, with a pattern of selectivity towards solid tumours that is not found in the reference alkaloid, the activity against the human lung carcinoma (A-549) being particularly noteworthy. The activities of meridine and compound as inhibitors of topoisomerase II were also significantly different.